首页 > 最新文献

Ophthalmic Genetics最新文献

英文 中文
Congenital glaucoma associated with high hyperopia, an ophthalmic phenotypical manifestation for GLIS3 deletion: case report and review of literature. 先天性青光眼伴高度远视,GLIS3缺失的眼科表型表现:病例报告及文献复习
IF 1 4区 医学 Q4 GENETICS & HEREDITY Pub Date : 2025-12-01 Epub Date: 2025-06-29 DOI: 10.1080/13816810.2025.2514526
Faeeqah Almhmoudi, Ghufran Abudawood, Arif O Khan, Ashraf Dallol, Naif Almontashiri, Amal Alhashem

Background: GLI-Similar 3 (GLIS3) gene plays a critical role in the regulation of several biological processes and is implicated in the development of various diseases. However, documentation regarding congenital glaucoma and other ophthalmic features in patients with GLIS3 variants is lacking. We aimed to expand the ophthalmological features related to GLIS3 deletion.

Methods: We present a case report of two Saudi Arabian siblings with congenital glaucoma, congenital diabetes mellitus, and congenital hypothyroidism. Full ophthalmological examination, medical evaluation, and genetic testing of all family members were conducted.

Results: In both patients, ophthalmic assessments revealed congenital glaucoma, high hyperopia, and short axial length of the globe. Genetic testing confirmed the presence of a large homozygous deletion, including the non-coding exon 1 and the entire coding exon 2 of the GLIS3 gene. Endocrine abnormalities included neonatal diabetes, congenital hypothyroidism, along with characteristic facial features that shows a long philtrum and thin and tight upper lip. Genetic testing of other siblings showed a heterozygous deletion of the GLIS3 gene. Although their ophthalmic examinations were unremarkable, all carriers presented with juvenile hypothyroidism.

Conclusion: Congenital glaucoma is commonly associated with myopia. We report an association between congenital glaucoma and high hyperopia related to GLIS3 partial deletion, which to our knowledge, has not been previously reported. We recommend that pediatric patients with neonatal diabetes and hypothyroidism to be evaluated for congenital glaucoma. Additionally, we suggest screening carriers for hypothyroidism.

背景:glii - similar 3 (GLIS3)基因在多种生物过程的调控中起关键作用,并与多种疾病的发生有关。然而,关于GLIS3变异患者的先天性青光眼和其他眼部特征的文献缺乏。我们的目的是扩大与GLIS3缺失相关的眼科特征。方法:我们报告了两个沙特阿拉伯的兄弟姐妹患有先天性青光眼、先天性糖尿病和先天性甲状腺功能减退症。对所有家庭成员进行了全面眼科检查、医学评估和基因检测。结果:两例患者的眼科检查均显示先天性青光眼、高度远视和眼球轴距短。基因检测证实存在一个大的纯合缺失,包括GLIS3基因的非编码外显子1和整个编码外显子2。内分泌异常包括新生儿糖尿病、先天性甲状腺功能减退、中长、上唇薄紧等特征。其他兄弟姐妹的基因检测显示GLIS3基因的杂合缺失。虽然眼科检查无显著差异,但所有携带者均表现为幼年性甲状腺功能减退。结论:先天性青光眼常与近视合并。我们报道先天性青光眼和高度远视之间与GLIS3部分缺失相关的关联,据我们所知,这在以前没有报道过。我们建议患有新生儿糖尿病和甲状腺功能减退症的儿童患者对先天性青光眼进行评估。此外,我们建议筛查甲状腺功能减退的携带者。
{"title":"Congenital glaucoma associated with high hyperopia, an ophthalmic phenotypical manifestation for <i>GLIS3</i> deletion: case report and review of literature.","authors":"Faeeqah Almhmoudi, Ghufran Abudawood, Arif O Khan, Ashraf Dallol, Naif Almontashiri, Amal Alhashem","doi":"10.1080/13816810.2025.2514526","DOIUrl":"10.1080/13816810.2025.2514526","url":null,"abstract":"<p><strong>Background: </strong>GLI-Similar 3 (<i>GLIS3</i>) gene plays a critical role in the regulation of several biological processes and is implicated in the development of various diseases. However, documentation regarding congenital glaucoma and other ophthalmic features in patients with <i>GLIS3</i> variants is lacking. We aimed to expand the ophthalmological features related to <i>GLIS3</i> deletion.</p><p><strong>Methods: </strong>We present a case report of two Saudi Arabian siblings with congenital glaucoma, congenital diabetes mellitus, and congenital hypothyroidism. Full ophthalmological examination, medical evaluation, and genetic testing of all family members were conducted.</p><p><strong>Results: </strong>In both patients, ophthalmic assessments revealed congenital glaucoma, high hyperopia, and short axial length of the globe. Genetic testing confirmed the presence of a large homozygous deletion, including the non-coding exon 1 and the entire coding exon 2 of the <i>GLIS3</i> gene. Endocrine abnormalities included neonatal diabetes, congenital hypothyroidism, along with characteristic facial features that shows a long philtrum and thin and tight upper lip. Genetic testing of other siblings showed a heterozygous deletion of the <i>GLIS3</i> gene. Although their ophthalmic examinations were unremarkable, all carriers presented with juvenile hypothyroidism.</p><p><strong>Conclusion: </strong>Congenital glaucoma is commonly associated with myopia. We report an association between congenital glaucoma and high hyperopia related to <i>GLIS3</i> partial deletion, which to our knowledge, has not been previously reported. We recommend that pediatric patients with neonatal diabetes and hypothyroidism to be evaluated for congenital glaucoma. Additionally, we suggest screening carriers for hypothyroidism.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"646-657"},"PeriodicalIF":1.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A novel NR2F1-associated microdeletion underlying Bosch-Boonstra-Schaaf optic atrophy syndrome. 一种新的nr2f1相关的微缺失可能导致Bosch-Boonstra-Schaaf视神经萎缩综合征。
IF 1 4区 医学 Q4 GENETICS & HEREDITY Pub Date : 2025-12-01 Epub Date: 2025-06-26 DOI: 10.1080/13816810.2025.2522365
Takaaki Hayashi, Kei Mizobuchi, Akiko Suga, Kazutoshi Yoshitake, Takeshi Iwata

Background: Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a rare autosomal dominant neurodevelopmental disorder that typically presents in early childhood. It is characterized by intellectual disability, developmental delay, and visual impairment, with optic atrophy being the most prominent ophthalmologic feature. The nuclear receptor subfamily 2, group F, member 1 (NR2F1) gene is currently the only known causative gene associated with BBSOAS. To date, no cases of BBSOAS have been reported in the Japanese population.

Cases presentation: We reported a 13-year-old Japanese male suspected of having BBSOAS, who presented with decreased visual acuity due to bilateral optic atrophy, as well as intellectual disability and developmental delay. Microarray-based comparative genomic hybridization (array-CGH), followed by whole-genome sequencing (WGS), identified a novel de novo 1.48-Mb heterozygous microdeletion involving NR2F1.

Conclusions: This is the first reported case of BBSOAS in a Japanese patient. These findings highlight the utility of array-CGH and WGS as powerful tools for detecting NR2F1-related microdeletions. BBSOAS should be considered in the differential diagnosis of patients presenting with developmental delay, intellectual disability, and visual impairment, even in the absence of a family history.

背景:Bosch-Boonstra-Schaaf视神经萎缩综合征(BBSOAS)是一种罕见的常染色体显性神经发育障碍,通常出现在儿童早期。它以智力障碍、发育迟缓和视力损害为特征,以视神经萎缩为最突出的眼科特征。核受体亚家族2,F组,成员1 (NR2F1)基因是目前唯一已知的与BBSOAS相关的致病基因。迄今为止,在日本人口中还没有报道过BBSOAS病例。病例介绍:我们报告了一名13岁的日本男性,怀疑患有BBSOAS,他表现为视力下降,由于双侧视神经萎缩,以及智力残疾和发育迟缓。基于微阵列的比较基因组杂交(array-CGH),随后进行全基因组测序(WGS),鉴定出一种新的涉及NR2F1的1.48 mb杂合微缺失。结论:这是日本患者首次报道的BBSOAS病例。这些发现强调了阵列- cgh和WGS作为检测nr2f1相关微缺失的强大工具的实用性。对于表现为发育迟缓、智力残疾和视力障碍的患者,即使没有家族史,也应考虑BBSOAS的鉴别诊断。
{"title":"A novel <i>NR2F1</i>-associated microdeletion underlying Bosch-Boonstra-Schaaf optic atrophy syndrome.","authors":"Takaaki Hayashi, Kei Mizobuchi, Akiko Suga, Kazutoshi Yoshitake, Takeshi Iwata","doi":"10.1080/13816810.2025.2522365","DOIUrl":"10.1080/13816810.2025.2522365","url":null,"abstract":"<p><strong>Background: </strong>Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a rare autosomal dominant neurodevelopmental disorder that typically presents in early childhood. It is characterized by intellectual disability, developmental delay, and visual impairment, with optic atrophy being the most prominent ophthalmologic feature. The <i>nuclear receptor subfamily 2, group F, member 1</i> (<i>NR2F1</i>) gene is currently the only known causative gene associated with BBSOAS. To date, no cases of BBSOAS have been reported in the Japanese population.</p><p><strong>Cases presentation: </strong>We reported a 13-year-old Japanese male suspected of having BBSOAS, who presented with decreased visual acuity due to bilateral optic atrophy, as well as intellectual disability and developmental delay. Microarray-based comparative genomic hybridization (array-CGH), followed by whole-genome sequencing (WGS), identified a novel <i>de novo</i> 1.48-Mb heterozygous microdeletion involving <i>NR2F1</i>.</p><p><strong>Conclusions: </strong>This is the first reported case of BBSOAS in a Japanese patient. These findings highlight the utility of array-CGH and WGS as powerful tools for detecting <i>NR2F1</i>-related microdeletions. BBSOAS should be considered in the differential diagnosis of patients presenting with developmental delay, intellectual disability, and visual impairment, even in the absence of a family history.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"671-674"},"PeriodicalIF":1.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Therapeutic benefit of idebenone in Leber hereditary optic neuropathy: a systematic review and meta-analysis. 依地苯酮治疗Leber遗传性视神经病变的疗效:系统回顾和荟萃分析。
IF 1 4区 医学 Q4 GENETICS & HEREDITY Pub Date : 2025-12-01 Epub Date: 2025-07-13 DOI: 10.1080/13816810.2025.2521647
Paulo Victor Zattar Ribeiro, Lucas Pari Mitre, Mateus M Gauza, Paulo Henrique Furukawa, Victor Evangelista De Faria Ferraz, Israel Gomy

Introduction: Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder characterized by the rapid loss of vision due to the degeneration of retinal ganglion cells. Current therapeutic options are limited. However, idebenone, a synthetic analog of coenzyme Q10, has shown promising neuroprotective properties. This systematic review and meta-analysis aim to evaluate the efficacy of idebenone in improving visual acuity in patients with LHON.

Methods: We performed a systematic review on PubMed, Cochrane, and Embase databases on 7 July 2024, for randomized and non-randomized studies analyzing the effect of idebenone on visual acuity in patients with LHON. Analyses were conducted using random-effects models. The main outcome of interest was visual acuity measured by the Logarithm of the Minimum Angle of Resolution (LogMAR). All statistical analyses were performed in R software version 4.3.2, using the "meta" and "metafor" packages. We registered the study on PROSPERO under protocol number CRD42024617308.

Results: Five studies (3 clinical trials and 2 retrospective cohorts) with 375 patients were included. The overall mean LogMAR difference was -0.32 (95% CI: -0.50 to -0.15), with a favorable effect of idebenone as compared to treatment without idebenone. This indicates a meaningful improvement in visual acuity with idebenone therapy, with changes translating to approximately 1.5-5 lines of better visual performance on the LogMAR scale.

Conclusion: This systematic review and meta-analysis found a substantial clinical improvement in visual acuity with idebenone therapy among patients with LHON.

Leber遗传性视神经病变(LHON)是一种线粒体疾病,其特征是由于视网膜神经节细胞变性而导致视力迅速丧失。目前的治疗选择有限。然而,依地苯酮,辅酶Q10的合成类似物,已经显示出有希望的神经保护特性。本系统综述和荟萃分析旨在评价依地苯酮改善LHON患者视力的疗效。方法:我们于2024年7月7日对PubMed、Cochrane和Embase数据库进行了系统综述,分析了依地苯酮对LHON患者视力的影响的随机和非随机研究。采用随机效应模型进行分析。主要结果是通过最小分辨角(LogMAR)的对数测量视力。所有统计分析均在R软件4.3.2版本中进行,使用“meta”和“metafor”包。我们注册了PROSPERO的研究,协议号为CRD42024617308。结果:纳入5项研究(3项临床试验和2项回顾性队列),共375例患者。总体平均LogMAR差异为-0.32 (95% CI: -0.50至-0.15),与不使用伊地苯酮的治疗相比,使用伊地苯酮的效果更好。这表明依地苯酮治疗对视力有显著改善,在LogMAR量表上,视力改善约为1.5-5线。结论:本系统综述和荟萃分析发现,依地苯酮治疗对LHON患者的视力有显著的临床改善。
{"title":"Therapeutic benefit of idebenone in Leber hereditary optic neuropathy: a systematic review and meta-analysis.","authors":"Paulo Victor Zattar Ribeiro, Lucas Pari Mitre, Mateus M Gauza, Paulo Henrique Furukawa, Victor Evangelista De Faria Ferraz, Israel Gomy","doi":"10.1080/13816810.2025.2521647","DOIUrl":"10.1080/13816810.2025.2521647","url":null,"abstract":"<p><strong>Introduction: </strong>Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder characterized by the rapid loss of vision due to the degeneration of retinal ganglion cells. Current therapeutic options are limited. However, idebenone, a synthetic analog of coenzyme Q10, has shown promising neuroprotective properties. This systematic review and meta-analysis aim to evaluate the efficacy of idebenone in improving visual acuity in patients with LHON.</p><p><strong>Methods: </strong>We performed a systematic review on PubMed, Cochrane, and Embase databases on 7 July 2024, for randomized and non-randomized studies analyzing the effect of idebenone on visual acuity in patients with LHON. Analyses were conducted using random-effects models. The main outcome of interest was visual acuity measured by the Logarithm of the Minimum Angle of Resolution (LogMAR). All statistical analyses were performed in R software version 4.3.2, using the \"meta\" and \"metafor\" packages. We registered the study on PROSPERO under protocol number CRD42024617308.</p><p><strong>Results: </strong>Five studies (3 clinical trials and 2 retrospective cohorts) with 375 patients were included. The overall mean LogMAR difference was -0.32 (95% CI: -0.50 to -0.15), with a favorable effect of idebenone as compared to treatment without idebenone. This indicates a meaningful improvement in visual acuity with idebenone therapy, with changes translating to approximately 1.5-5 lines of better visual performance on the LogMAR scale.</p><p><strong>Conclusion: </strong>This systematic review and meta-analysis found a substantial clinical improvement in visual acuity with idebenone therapy among patients with LHON.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"517-522"},"PeriodicalIF":1.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bilateral retinal dystrophy and unilateral hearing loss caused by mosaic phosphoribosyl pyrophosphate synthetase 1 deficiency: expanding the spectrum of an ultrarare neurometabolic disorder. 马赛克磷酸核糖基焦磷酸合成酶1缺乏引起的双侧视网膜营养不良和单侧听力丧失:扩大了一种罕见神经代谢疾病的频谱。
IF 1 4区 医学 Q4 GENETICS & HEREDITY Pub Date : 2025-12-01 Epub Date: 2025-08-07 DOI: 10.1080/13816810.2025.2543157
Pankaj Prasun, Elizabeth Kellom, Kimberly Stepien

Background: Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) deficiency is a rare neurometabolic disorder with wide spectrum of presentation. It can present in early childhood with global developmental delay, retinal dystrophy, and hearing loss, or can present as isolated neuropathy or hearing loss in adulthood. Here we describe a patient with vision impairment, fatigue, and unilateral hearing loss caused by a somatic mosaic pathogenic variant in PRPS1 gene which encodes PRPS1. Supplementation with S-adenosylmethionine (SAMe) and Nicotinamide Riboside (NR) resulted in improvement in symptoms.

Method and results: This retrospective clinical-laboratory observational study has a reference patient who was found to have right-sided hearing loss and vision impairment in right eye in early childhood. Later on, he developed epilepsy. He had deterioration in cognitive function in adolescence. At the age of 26 years, he developed progressive vision impairment due to bilateral, asymmetric retinal degeneration. In addition, he had severe generalized fatigue. Molecular diagnostic workup showed a mosaic pathogenic variant c.383A > T, p. Asp128Val in PRPS1. Subsequently, SAMe at 800mg twice a day and NR at 800 mg daily doses were started leading to significant improvement in fatigue and stabilization of vision.

Conclusion: PRPS1 deficiency is an inherited disease of nucleotide biosynthesis. The age of onset of symptoms as well as severity of symptoms are variable. Supplementations with nucleotide precursors may stabilize the clinical course.

背景:磷酸核糖基焦磷酸合成酶1 (PRPS1)缺乏症是一种罕见的神经代谢性疾病,表现广泛。它可以在儿童早期表现为整体发育迟缓、视网膜营养不良和听力丧失,也可以在成年期表现为孤立的神经病变或听力丧失。在这里,我们描述了一位由PRPS1基因的体细胞马赛克致病性变异引起的视力障碍,疲劳和单侧听力丧失的患者,该基因编码PRPS1。补充s -腺苷蛋氨酸(SAMe)和烟酰胺核苷(NR)可改善症状。方法与结果:本回顾性临床-实验室观察性研究有1例儿童早期发现右眼听力丧失和右眼视力障碍的参考患者。后来,他患上了癫痫。他在青少年时期认知功能退化。26岁时,由于双侧不对称视网膜变性,他出现了进行性视力障碍。此外,他有严重的全身疲劳。分子诊断结果显示,PRPS1中存在花叶致病变异c.383A > T, p. Asp128Val。随后,SAMe剂量为800mg,每天两次,NR剂量为800mg,导致疲劳和视力稳定的显著改善。结论:PRPS1缺乏症是一种遗传性核苷酸生物合成疾病。症状出现的年龄以及症状的严重程度是可变的。补充核苷酸前体可以稳定临床病程。
{"title":"Bilateral retinal dystrophy and unilateral hearing loss caused by mosaic phosphoribosyl pyrophosphate synthetase 1 deficiency: expanding the spectrum of an ultrarare neurometabolic disorder.","authors":"Pankaj Prasun, Elizabeth Kellom, Kimberly Stepien","doi":"10.1080/13816810.2025.2543157","DOIUrl":"10.1080/13816810.2025.2543157","url":null,"abstract":"<p><strong>Background: </strong>Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) deficiency is a rare neurometabolic disorder with wide spectrum of presentation. It can present in early childhood with global developmental delay, retinal dystrophy, and hearing loss, or can present as isolated neuropathy or hearing loss in adulthood. Here we describe a patient with vision impairment, fatigue, and unilateral hearing loss caused by a somatic mosaic pathogenic variant in PRPS1 gene which encodes PRPS1. Supplementation with S-adenosylmethionine (SAMe) and Nicotinamide Riboside (NR) resulted in improvement in symptoms.</p><p><strong>Method and results: </strong>This retrospective clinical-laboratory observational study has a reference patient who was found to have right-sided hearing loss and vision impairment in right eye in early childhood. Later on, he developed epilepsy. He had deterioration in cognitive function in adolescence. At the age of 26 years, he developed progressive vision impairment due to bilateral, asymmetric retinal degeneration. In addition, he had severe generalized fatigue. Molecular diagnostic workup showed a mosaic pathogenic variant c.383A > T, p. Asp128Val in PRPS1. Subsequently, SAMe at 800mg twice a day and NR at 800 mg daily doses were started leading to significant improvement in fatigue and stabilization of vision.</p><p><strong>Conclusion: </strong>PRPS1 deficiency is an inherited disease of nucleotide biosynthesis. The age of onset of symptoms as well as severity of symptoms are variable. Supplementations with nucleotide precursors may stabilize the clinical course.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"697-701"},"PeriodicalIF":1.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A novel missense TUBB4B variant outside of the canonical hotspot is associated with cone-rod dystrophy and sensorineural hearing loss. 典型热点外的一种新的错义TUBB4B变体与锥杆营养不良和感音神经性听力损失有关。
IF 1 4区 医学 Q4 GENETICS & HEREDITY Pub Date : 2025-12-01 Epub Date: 2025-10-07 DOI: 10.1080/13816810.2025.2565651
Lauren Y Cao, Anna Duemler, Emily H Jung, Ramiro S Maldonado, Sarah Richards, Elena R Schiff, Omar A Mahroo, Andrew R Webster, Siying Lin, Beau J Fenner, Alessandro Iannaccone, Oleg Alekseev

Introduction: Pathogenic variants in TUBB4B, which encodes the β-tubulin 4B isotype of microtubule subunits, have been associated with Leber congenital amaurosis with early-onset deafness (LCAEOD), an autosomal dominant condition characterized by early and severe loss of photoreceptor and cochlear cells. The majority of reported cases feature early disease onset and are caused by missense mutations in the R390/R391 hotspot.

Methods: Multimodal evaluation included ultra-widefield pseudocolor and autofluorescence fundus photography, spectral-domain optical coherence tomography, full-field electroretinography, Goldmann kinetic perimetry, audiography, and genetic testing with next-generation sequencing.

Results: We report seven individuals from three unrelated families affected by cone-rod dystrophy and sensorineural hearing loss associated with a novel variant in TUBB4B (c.784C > T, p.R262W). Cone-rod dystrophy associated with this variant generally features a later age of onset compared to the Leber congenital amaurosis caused by variants in the canonical hotspot.

Discussion: This report expands the mutation spectrum and phenotypic range of TUBB4B-associated retinopathies beyond the R390/R391 hotspot and may offer insight into the pathogenesis of this rare tubulinopathy.

TUBB4B的致病变异编码微管亚基β-微管蛋白4B同型,与Leber先天性黑蒙伴早发性耳聋(LCAEOD)有关,LCAEOD是一种常染色体显性遗传病,以早期和严重的光感受器和耳蜗细胞丧失为特征。大多数报告的病例以早期发病为特征,是由R390/R391热点的错义突变引起的。方法:多模式评估包括超宽视场假彩色和自体荧光眼底摄影、光谱域光学相干断层扫描、全视场视网膜电图、Goldmann动力学视野、听力学和下一代测序基因检测。结果:我们报告了来自三个不相关家族的7名患者,他们患有与TUBB4B基因新变异相关的锥杆营养不良和感音神经性听力损失(c.784C . > T, p.R262W)。与典型热点变异引起的Leber先天性黑朦相比,与这种变异相关的锥杆营养不良通常具有发病年龄较晚的特点。讨论:本报告扩展了R390/R391热点之外的tubb4b相关视网膜病变的突变谱和表型范围,并可能为这种罕见的小管病变的发病机制提供见解。
{"title":"A novel missense <i>TUBB4B</i> variant outside of the canonical hotspot is associated with cone-rod dystrophy and sensorineural hearing loss.","authors":"Lauren Y Cao, Anna Duemler, Emily H Jung, Ramiro S Maldonado, Sarah Richards, Elena R Schiff, Omar A Mahroo, Andrew R Webster, Siying Lin, Beau J Fenner, Alessandro Iannaccone, Oleg Alekseev","doi":"10.1080/13816810.2025.2565651","DOIUrl":"10.1080/13816810.2025.2565651","url":null,"abstract":"<p><strong>Introduction: </strong>Pathogenic variants in TUBB4B, which encodes the β-tubulin 4B isotype of microtubule subunits, have been associated with Leber congenital amaurosis with early-onset deafness (LCAEOD), an autosomal dominant condition characterized by early and severe loss of photoreceptor and cochlear cells. The majority of reported cases feature early disease onset and are caused by missense mutations in the R390/R391 hotspot.</p><p><strong>Methods: </strong>Multimodal evaluation included ultra-widefield pseudocolor and autofluorescence fundus photography, spectral-domain optical coherence tomography, full-field electroretinography, Goldmann kinetic perimetry, audiography, and genetic testing with next-generation sequencing.</p><p><strong>Results: </strong>We report seven individuals from three unrelated families affected by cone-rod dystrophy and sensorineural hearing loss associated with a novel variant in TUBB4B (c.784C > T, p.R262W). Cone-rod dystrophy associated with this variant generally features a later age of onset compared to the Leber congenital amaurosis caused by variants in the canonical hotspot.</p><p><strong>Discussion: </strong>This report expands the mutation spectrum and phenotypic range of TUBB4B-associated retinopathies beyond the R390/R391 hotspot and may offer insight into the pathogenesis of this rare tubulinopathy.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"594-603"},"PeriodicalIF":1.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neuro-ophthalmic complications of endosteal hyperostosis, Worth type: the importance of ophthalmic monitoring. 内膜肥大症的神经-眼并发症,Worth型:眼科监测的重要性。
IF 1 4区 医学 Q4 GENETICS & HEREDITY Pub Date : 2025-12-01 Epub Date: 2025-08-26 DOI: 10.1080/13816810.2025.2535985
Aisling Higham, Laura M Watts, Dipesh Rao, Paul Wordsworth, Darius Hildebrand, David Johnson, Deborah Shears

Disorders of bone formation or resorption affecting the cranium can lead to ophthalmic complications. We describe a family with Worth endosteal hyperostosis (WEH), an autosomal dominant condition characterized by mandibular overgrowth and cortical thickening of long bones. Although traditionally considered benign, we report significant neuro-ophthalmic complications in this kindred.This retrospective case series examines a two-generation family of three siblings and their mother, all with clinical features of WEH and a confirmed lipoprotein-related protein 5 (LRP5) gene mutation. A literature review is also included.The proband was diagnosed with WEH after an incidental finding of dense bones on a chest x-ray at age 16, with no neurological complications. However, her three affected children developed papilledema due to elevated intracranial pressure, requiring calvarial expansion. Computed tomography imaging revealed calvarial thickening and late-onset sagittal synostosis in two individuals. In two cases, intracranial hypertension was detected only after routine ophthalmic monitoring revealed papilledema. All had successful outcomes with resolution of papilledema following surgery.Here, we show that WEH can be associated with serious and late onset neuro-ophthalmic manifestations and secondary sagittal synostosis. We recommend regular ophthalmic review to facilitate early detection of potential complications, as part of the multidisciplinary care.

影响颅骨的骨形成或骨吸收障碍可导致眼部并发症。我们描述了一个家族与沃思骨膜肥大(WEH),常染色体显性条件的特点是下颌骨过度生长和长骨皮质增厚。虽然传统上认为是良性的,我们报告了显著的神经眼科并发症。本回顾性病例系列研究了一个两代家庭,包括三个兄弟姐妹及其母亲,均具有WEH的临床特征和确认的脂蛋白相关蛋白5 (LRP5)基因突变。文献综述也包括在内。该先证者16岁时在胸部x光片上偶然发现致密骨骼后被诊断为WEH,没有神经系统并发症。然而,她的三个受影响的孩子由于颅内压升高而发展为乳头水肿,需要颅骨扩张。计算机断层成像显示颅骨增厚和迟发性矢状关节闭锁在两个个体。在两例中,只有在常规眼科监测显示乳头水肿后才发现颅内高压。所有患者手术后乳头水肿均得到缓解。在这里,我们发现WEH可能与严重和晚发的神经-眼表现和继发性矢状面结膜紧闭有关。我们建议定期眼科检查,以促进早期发现潜在的并发症,作为多学科护理的一部分。
{"title":"Neuro-ophthalmic complications of endosteal hyperostosis, Worth type: the importance of ophthalmic monitoring.","authors":"Aisling Higham, Laura M Watts, Dipesh Rao, Paul Wordsworth, Darius Hildebrand, David Johnson, Deborah Shears","doi":"10.1080/13816810.2025.2535985","DOIUrl":"10.1080/13816810.2025.2535985","url":null,"abstract":"<p><p>Disorders of bone formation or resorption affecting the cranium can lead to ophthalmic complications. We describe a family with Worth endosteal hyperostosis (WEH), an autosomal dominant condition characterized by mandibular overgrowth and cortical thickening of long bones. Although traditionally considered benign, we report significant neuro-ophthalmic complications in this kindred.This retrospective case series examines a two-generation family of three siblings and their mother, all with clinical features of WEH and a confirmed lipoprotein-related protein 5 (<i>LRP5)</i> gene mutation. A literature review is also included.The proband was diagnosed with WEH after an incidental finding of dense bones on a chest x-ray at age 16, with no neurological complications. However, her three affected children developed papilledema due to elevated intracranial pressure, requiring calvarial expansion. Computed tomography imaging revealed calvarial thickening and late-onset sagittal synostosis in two individuals. In two cases, intracranial hypertension was detected only after routine ophthalmic monitoring revealed papilledema. All had successful outcomes with resolution of papilledema following surgery.Here, we show that WEH can be associated with serious and late onset neuro-ophthalmic manifestations and secondary sagittal synostosis. We recommend regular ophthalmic review to facilitate early detection of potential complications, as part of the multidisciplinary care.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"688-691"},"PeriodicalIF":1.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ocular manifestations of trisomy 8 mosaicim: a rare case report. 8号三体镶嵌病的眼部表现:1例罕见报告。
IF 1 4区 医学 Q4 GENETICS & HEREDITY Pub Date : 2025-12-01 Epub Date: 2025-11-03 DOI: 10.1080/13816810.2025.2579719
Faisal A Altahan, Reem A AlAbdulqader

Background: Trisomy 8 mosaicism (T8M) also known as Warkany syndrome 2 is a rare chromosomal disorder characterized by a highly variable phenotypic presentation. Ranging from mild congenital anomalies to life and sight threatening associations. Currently, the most common ophthalmic manifestations are strabismus, hypertelorism, and corneal opacities. Other visually debilitating features include microphthalmia, retinal dystrophy, and optic disc coloboma.

Case presentation: We present a case of a 9-year-old male who was referred to our ophthalmology service as a case of strabismus and bilateral ptosis with syndromic facial features of a protruded jaw, low set ears, and wide nasal bridge, and was later confirmed with cytogenetic analysis of T8M. To the best of our knowledge, this is the first reported case of T8M in our region, and the first to present euryblepharon as an associated ophthalmic manifestation, in addition to providing an updated review of the most commonly and newly documented manifestations of T8M.

Conclusion: The phenotypic variation of T8M is diverse and often unpredictable, ranging from mild ocular findings to visually debilitating manifestations. Comprehensive awareness of its ophthalmic features can aid ophthalmologists in early recognition and appropriate genetic evaluation and counseling.

背景:8号三体嵌合体(T8M)也被称为Warkany综合征2,是一种罕见的染色体疾病,其特征是表型表现高度可变。从轻微的先天性异常到威胁生命和视力的关联。目前,最常见的眼部表现为斜视、远视和角膜混浊。其他使视力衰弱的特征包括小眼症、视网膜营养不良和视盘缺损。病例介绍:我们报告了一个9岁的男性病例,他被转到我们的眼科部门,作为斜视和双侧上睑下垂的病例,他的面部特征是下巴突出,耳朵低,鼻梁宽,后来通过细胞遗传学分析证实了T8M。据我们所知,这是我们地区第一例报道的T8M病例,也是第一例将泛睑下垂作为一种相关的眼科表现,此外还提供了对T8M最常见和最新记录的表现的最新回顾。结论:T8M的表型变异是多样的,通常是不可预测的,从轻微的眼部表现到视力衰弱的表现。全面了解其眼科特征可以帮助眼科医生早期识别和适当的遗传评估和咨询。
{"title":"Ocular manifestations of trisomy 8 mosaicim: a rare case report.","authors":"Faisal A Altahan, Reem A AlAbdulqader","doi":"10.1080/13816810.2025.2579719","DOIUrl":"10.1080/13816810.2025.2579719","url":null,"abstract":"<p><strong>Background: </strong>Trisomy 8 mosaicism (T8M) also known as Warkany syndrome 2 is a rare chromosomal disorder characterized by a highly variable phenotypic presentation. Ranging from mild congenital anomalies to life and sight threatening associations. Currently, the most common ophthalmic manifestations are strabismus, hypertelorism, and corneal opacities. Other visually debilitating features include microphthalmia, retinal dystrophy, and optic disc coloboma.</p><p><strong>Case presentation: </strong>We present a case of a 9-year-old male who was referred to our ophthalmology service as a case of strabismus and bilateral ptosis with syndromic facial features of a protruded jaw, low set ears, and wide nasal bridge, and was later confirmed with cytogenetic analysis of T8M. To the best of our knowledge, this is the first reported case of T8M in our region, and the first to present euryblepharon as an associated ophthalmic manifestation, in addition to providing an updated review of the most commonly and newly documented manifestations of T8M.</p><p><strong>Conclusion: </strong>The phenotypic variation of T8M is diverse and often unpredictable, ranging from mild ocular findings to visually debilitating manifestations. Comprehensive awareness of its ophthalmic features can aid ophthalmologists in early recognition and appropriate genetic evaluation and counseling.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"532-537"},"PeriodicalIF":1.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145438703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corneal parameters in pediatric triple a syndrome patients with alacrima. 小儿三甲综合征伴泪斑的角膜参数分析。
IF 1 4区 医学 Q4 GENETICS & HEREDITY Pub Date : 2025-12-01 Epub Date: 2025-08-04 DOI: 10.1080/13816810.2025.2538560
Miray Faiz Turan, Ihsan Turan

Introduction: To evaluate the changes in central corneal thickness and curvature parameters in pediatric patients with Triple A syndrome and alacrima.

Methods: This retrospective study included 52 eyes of 26 patients with Triple A syndrome. All patients had alacrima. Pentacam was used to analyze the keratometry in the flat (K1) and steep meridian (K2) and maximum keratometry (Kmax), mean keratometry (Kmean) readings, central corneal thickness at the vertex (CCT) and at the thinnest point (CCT-TP) were recorded. Patients were divided into three groups based on their age (Group 1: 3-6 years, group 2: 7-12 years, group 3: 13-18 years). Values were compared between pediatric patients with Triple A and normal controls.

Results: The K1 values of all patients were significantly higher than those observed in healthy data (p < 0.001). 15 Group 1 had significantly lower K2 and higher CCT values (p = 0.008, p = 0.015). In group 2, K1 and Kmax were significantly higher, while CCT and CCT-TP were lower (p = 0.016, p < 0.001, p < 0.001, p < 0.001, respectively). In group 3, K1 and CCT and CCT-TP were significantly higher than the normal data (p = 0.019, p < 0.001, p < 0.001, respectively).

Discussion: Since dry eye syndrome may cause corneal changes, in AAAS patients, corneal topographic variations may occur due to alacrima. Thus, these patients should be evaluated during follow-up visits.

前言:探讨小儿aaa综合征合并白斑患者角膜中央厚度和曲率参数的变化。方法:对26例aaa综合征患者52眼进行回顾性研究。所有患者均有白斑。用Pentacam分析平子午线(K1)和陡子午线(K2)的角膜密度,并记录最大角膜密度(Kmax)、平均角膜密度(Kmean)读数、顶点中心角膜厚度(CCT)和最薄点角膜厚度(CCT- tp)。根据患者年龄分为3组(1组3 ~ 6岁,2组7 ~ 12岁,3组13 ~ 18岁)。比较了aaa患儿与正常对照的数值。结果:所有患者的K1值均显著高于健康组(p < 0.001)。1组患者K2显著降低,CCT显著升高(p = 0.008, p = 0.015)。2组K1和Kmax显著升高,CCT和CCT- tp显著降低(p = 0.016, p < 0.001, p < 0.001, p < 0.001)。3组K1、CCT、CCT- tp均显著高于正常组(p = 0.019, p < 0.001, p < 0.001)。讨论:由于干眼综合征可引起角膜改变,在AAAS患者中,角膜白斑可能导致角膜地形变化。因此,这些患者应在随访时进行评估。
{"title":"Corneal parameters in pediatric triple a syndrome patients with alacrima.","authors":"Miray Faiz Turan, Ihsan Turan","doi":"10.1080/13816810.2025.2538560","DOIUrl":"10.1080/13816810.2025.2538560","url":null,"abstract":"<p><strong>Introduction: </strong>To evaluate the changes in central corneal thickness and curvature parameters in pediatric patients with Triple A syndrome and alacrima.</p><p><strong>Methods: </strong>This retrospective study included 52 eyes of 26 patients with Triple A syndrome. All patients had alacrima. Pentacam was used to analyze the keratometry in the flat (K1) and steep meridian (K2) and maximum keratometry (Kmax), mean keratometry (Kmean) readings, central corneal thickness at the vertex (CCT) and at the thinnest point (CCT-TP) were recorded. Patients were divided into three groups based on their age (Group 1: 3-6 years, group 2: 7-12 years, group 3: 13-18 years). Values were compared between pediatric patients with Triple A and normal controls.</p><p><strong>Results: </strong>The K1 values of all patients were significantly higher than those observed in healthy data (<i>p</i> < 0.001). 15 Group 1 had significantly lower K2 and higher CCT values (<i>p</i> = 0.008, <i>p</i> = 0.015). In group 2, K1 and Kmax were significantly higher, while CCT and CCT-TP were lower (<i>p</i> = 0.016, <i>p</i> < 0.001, <i>p</i> < 0.001, <i>p</i> < 0.001, respectively). In group 3, K1 and CCT and CCT-TP were significantly higher than the normal data (<i>p</i> = 0.019, <i>p</i> < 0.001, <i>p</i> < 0.001, respectively).</p><p><strong>Discussion: </strong>Since dry eye syndrome may cause corneal changes, in AAAS patients, corneal topographic variations may occur due to alacrima. Thus, these patients should be evaluated during follow-up visits.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"576-580"},"PeriodicalIF":1.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A genotype to phenotype relationship of exudative vitreoretinopathy in Loeys-Dietz syndrome due to a pathogenic variant in TGFBR2. 由TGFBR2致病变异引起的Loeys-Dietz综合征渗出性玻璃体视网膜病变的基因型与表型关系
IF 1 4区 医学 Q4 GENETICS & HEREDITY Pub Date : 2025-12-01 Epub Date: 2025-09-29 DOI: 10.1080/13816810.2025.2565633
Mark Lindquist, Viridiana Hernandez-Lopez, Debarshi Mustafi

Introduction: Loeys-Dietz syndrome (LDS) is a rare autosomal dominant connective tissue disorder most commonly due to pathogenic variants in the transforming growth factor beta receptor genes TGFBR1 and TGFBR2. There have been reports of a few sporadic cases of LDS patients exhibiting a vitreoretinopathy phenotype due to pathogenic variants in the TGFBR2 gene.

Case presentation: We report a 13-year-old female with LDS who harbored a de novo pathogenic missense variant (c.1582C>T, p.Arg528Cys) in TGFBR2. She presented with reduced visual acuity in the right eye due to a vitreous hemorrhage. Fluorescein angiography identified neovascularization in the right eye with peripheral avascular retina in both eyes. These phenotypic features were similar to those seen in familial exudative vitreoretinopathy (FEVR). Intravitreal anti-VEGF treatment in the right eye led to visual improvement, followed by laser photocoagulation of the peripheral retina of both eyes to mitigate future complications.

Discussion: This is the second reported case of a missense variant at the amino acid residue 528 (Arg528) of TGFBR2 that results in a FEVR-like phenotype in a LDS patient. In silico protein prediction and machine learning analyses of the affected region of the TGFBR2 protein suggest this missense variant disrupts the protein kinase domain. We hypothesize this change influences the Wnt/beta-catenin pathway, leading to abnormal retinal vasculogenesis.

Conclusions: This case highlights the importance of a genotype to phenotype relationship in LDS and suggests that certain variants in TGFBR2 may predispose to vitreoretinopathy. Recognition of this is important as timely anti-VEGF and laser intervention can limit visual threatening complications.

简介:Loeys-Dietz综合征(LDS)是一种罕见的常染色体显性结缔组织疾病,最常见的原因是转化生长因子受体基因TGFBR1和TGFBR2的致病性变异。有报道称,一些散发性LDS患者由于TGFBR2基因的致病变异而表现出玻璃体视网膜病变表型。病例介绍:我们报告了一名13岁的LDS女性,她携带TGFBR2的新发致病性错义变异(c.1582C>T, p.Arg528Cys)。由于玻璃体出血,她右眼视力下降。荧光素血管造影发现右眼新生血管,双眼周围无血管视网膜。这些表型特征与家族性渗出性玻璃体视网膜病变(FEVR)相似。右眼玻璃体内抗vegf治疗可改善视力,随后对双眼周围视网膜进行激光光凝以减轻未来并发症。讨论:这是第二例报道的TGFBR2氨基酸残基528 (Arg528)错义变异,导致LDS患者出现fevr样表型。对TGFBR2蛋白受影响区域的硅蛋白预测和机器学习分析表明,这种错义变体破坏了蛋白激酶结构域。我们假设这种变化影响Wnt/ β -连环蛋白通路,导致视网膜血管生成异常。结论:该病例强调了LDS中基因型与表型关系的重要性,并提示TGFBR2的某些变异可能易导致玻璃体视网膜病变。认识到这一点很重要,因为及时的抗vegf和激光干预可以限制威胁视力的并发症。
{"title":"A genotype to phenotype relationship of exudative vitreoretinopathy in Loeys-Dietz syndrome due to a pathogenic variant in <i>TGFBR2</i>.","authors":"Mark Lindquist, Viridiana Hernandez-Lopez, Debarshi Mustafi","doi":"10.1080/13816810.2025.2565633","DOIUrl":"10.1080/13816810.2025.2565633","url":null,"abstract":"<p><strong>Introduction: </strong>Loeys-Dietz syndrome (LDS) is a rare autosomal dominant connective tissue disorder most commonly due to pathogenic variants in the transforming growth factor beta receptor genes <i>TGFBR1</i> and <i>TGFBR2</i>. There have been reports of a few sporadic cases of LDS patients exhibiting a vitreoretinopathy phenotype due to pathogenic variants in the TGFBR2 gene.</p><p><strong>Case presentation: </strong>We report a 13-year-old female with LDS who harbored a de novo pathogenic missense variant (c.1582C>T, p.Arg528Cys) in <i>TGFBR2</i>. She presented with reduced visual acuity in the right eye due to a vitreous hemorrhage. Fluorescein angiography identified neovascularization in the right eye with peripheral avascular retina in both eyes. These phenotypic features were similar to those seen in familial exudative vitreoretinopathy (FEVR). Intravitreal anti-VEGF treatment in the right eye led to visual improvement, followed by laser photocoagulation of the peripheral retina of both eyes to mitigate future complications.</p><p><strong>Discussion: </strong>This is the second reported case of a missense variant at the amino acid residue 528 (Arg528) of <i>TGFBR2</i> that results in a FEVR-like phenotype in a LDS patient. In silico protein prediction and machine learning analyses of the affected region of the <i>TGFBR2</i> protein suggest this missense variant disrupts the protein kinase domain. We hypothesize this change influences the Wnt/beta-catenin pathway, leading to abnormal retinal vasculogenesis.</p><p><strong>Conclusions: </strong>This case highlights the importance of a genotype to phenotype relationship in LDS and suggests that certain variants in <i>TGFBR2</i> may predispose to vitreoretinopathy. Recognition of this is important as timely anti-VEGF and laser intervention can limit visual threatening complications.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"713-716"},"PeriodicalIF":1.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Membrane frizzled-related protein: a comprehensive analysis of genetic characteristics, phenotypic manifestations and impact on retinal microvasculature. 膜卷曲相关蛋白:遗传特征、表型表现及对视网膜微血管影响的综合分析。
IF 1 4区 医学 Q4 GENETICS & HEREDITY Pub Date : 2025-12-01 Epub Date: 2025-10-02 DOI: 10.1080/13816810.2025.2566428
Metehan Simsek, Merve Ozbek, Selim Ayata, Oguzhan Yarali, Yusuf Alperen Yarali, Ozgur Artunay

Purpose: To assess the ocular characteristics, retinal microvasculature, and long-term outcomes of patients with nanophthalmos associated with mutations in the membrane frizzled-related protein (MFRP) gene, and to compare these findings with those observed in nanophthalmos cases without MFRP gene mutations.

Methods: In this retrospective cohort study, patients with MFRP-associated nanophthalmos and those with nanophthalmos without MFRP gene mutations were included. Best-corrected visual acuity (BCVA), spherical equivalent (SE), axial length (AL), optical coherence tomography (OCT), and OCT angiography parameters-including vascular density (VD) and foveal avascular zone (FAZ) measurements in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC)-were evaluated at presentation and at the 5th-year follow-up.

Results: At presentation and 5-year follow-up, patients with MFRP-associated nanophthalmos exhibited significantly shorter AL and higher SE compared to those without MFRP mutations (all p < 0.001). Central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and retinal nerve fiber layer (RNFL) thickness were significantly greater in the MFRP-associated group at presentation and 5-year follow-up (all p < 0.05). OCT angiography revealed reduced parafoveal VD in the SCP and DCP, as well as decreased foveal and parafoveal VD in the CC in the MFRP group compared to the group without MFRP mutations (all p < 0.05). FAZ areas in the SCP and DCP were also significantly smaller in the MFRP group (p < 0.001 and p = 0.01, respectively).

Conclusions: Eyes with MFRP-associated nanophthalmos exhibit significantly higher SE, shorter AL, and more pronounced alterations in retinal structure and microvasculature compared with eyes without MFRP mutations.

目的:评估与膜卷曲相关蛋白(MFRP)基因突变相关的纳米眼患者的眼部特征、视网膜微血管和长期预后,并将这些结果与未发生MFRP基因突变的纳米眼患者进行比较。方法:回顾性队列研究纳入MFRP相关纳米眼患者和未发生MFRP基因突变的纳米眼患者。最佳矫正视力(BCVA),球面等效(SE),轴向长度(AL),光学相干断层扫描(OCT),和OCT血管造影参数-包括血管密度(VD)和中央凹无血管带(FAZ)测量在浅毛细血管丛(SCP),深毛细血管丛(DCP),绒毛膜毛细血管(CC)-在就诊时和第5年随访时进行评估。结果:在就诊和5年随访中,与未发生MFRP突变的患者相比,MFRP相关的纳米眼患者表现出明显更短的AL和更高的SE(均p p p p p = 0.01)。结论:与没有MFRP突变的眼睛相比,MFRP相关的纳米眼具有明显更高的SE,更短的AL,以及更明显的视网膜结构和微血管改变。
{"title":"Membrane frizzled-related protein: a comprehensive analysis of genetic characteristics, phenotypic manifestations and impact on retinal microvasculature.","authors":"Metehan Simsek, Merve Ozbek, Selim Ayata, Oguzhan Yarali, Yusuf Alperen Yarali, Ozgur Artunay","doi":"10.1080/13816810.2025.2566428","DOIUrl":"10.1080/13816810.2025.2566428","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the ocular characteristics, retinal microvasculature, and long-term outcomes of patients with nanophthalmos associated with mutations in the membrane frizzled-related protein (MFRP) gene, and to compare these findings with those observed in nanophthalmos cases without MFRP gene mutations.</p><p><strong>Methods: </strong>In this retrospective cohort study, patients with MFRP-associated nanophthalmos and those with nanophthalmos without MFRP gene mutations were included. Best-corrected visual acuity (BCVA), spherical equivalent (SE), axial length (AL), optical coherence tomography (OCT), and OCT angiography parameters-including vascular density (VD) and foveal avascular zone (FAZ) measurements in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC)-were evaluated at presentation and at the 5th-year follow-up.</p><p><strong>Results: </strong>At presentation and 5-year follow-up, patients with MFRP-associated nanophthalmos exhibited significantly shorter AL and higher SE compared to those without MFRP mutations (all <i>p</i> < 0.001). Central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and retinal nerve fiber layer (RNFL) thickness were significantly greater in the MFRP-associated group at presentation and 5-year follow-up (all <i>p</i> < 0.05). OCT angiography revealed reduced parafoveal VD in the SCP and DCP, as well as decreased foveal and parafoveal VD in the CC in the MFRP group compared to the group without MFRP mutations (all <i>p</i> < 0.05). FAZ areas in the SCP and DCP were also significantly smaller in the MFRP group (<i>p</i> < 0.001 and <i>p</i> = 0.01, respectively).</p><p><strong>Conclusions: </strong>Eyes with MFRP-associated nanophthalmos exhibit significantly higher SE, shorter AL, and more pronounced alterations in retinal structure and microvasculature compared with eyes without MFRP mutations.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"604-613"},"PeriodicalIF":1.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Ophthalmic Genetics
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1