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Congenital Heart Defects and 22q11.2 Deletion Syndrome: A 20-Year Update and New Insights to Aid Clinical Diagnosis. 先天性心脏缺陷和 22q11.2 缺失综合征:先天性心脏缺陷和 22q11.2 缺失综合征:20 年来的最新进展和有助于临床诊断的新见解》(A 20-Year Update and New Insights to Aid Clinical Diagnosis.
IF 0.4 Pub Date : 2023-02-17 eCollection Date: 2023-06-01 DOI: 10.1055/s-0043-1763258
Bruna Lixinski Diniz, Desirée Deconte, Kerolainy Alves Gadelha, Andressa Barreto Glaeser, Bruna Baierle Guaraná, Andreza Ávila de Moura, Rafael Fabiano Machado Rosa, Paulo Ricardo Gazzola Zen

Congenital heart defects (CHDs) are one of the most prevalent clinical features described in individuals diagnosed with 22q11.2 deletion syndrome (22q11.2DS). Therefore, cardiac malformations may be the main finding to refer for syndrome investigation, especially in individuals with a mild phenotype. Nowadays, different cytogenetic methodologies have emerged and are used routinely in research laboratories. Hence, choosing an efficient technology and providing an accurate interpretation of clinical findings is crucial for 22q11.2DS patient's diagnosis. This systematic review provides an update of the last 20 years of research on 22q11.2DS patients with CHD and the investigation process behind each diagnosis. A search was performed in PubMed, Embase, and LILACS using all entry terms to DiGeorge syndrome, CHDs, and cytogenetic analysis. After screening, 60 papers were eligible for review. We present a new insight of ventricular septal defect as a possible pivotal cardiac finding in individuals with 22q11.2DS. Also, we describe molecular technologies and cardiac evaluation as valuable tools in order to guide researchers in future investigations.

先天性心脏缺陷(CHDs)是被诊断为 22q11.2 缺失综合征(22q11.2DS)患者最常见的临床特征之一。因此,心脏畸形可能是综合征调查的主要发现,尤其是在表型轻微的个体中。如今,不同的细胞遗传学方法已经出现,并被研究实验室常规使用。因此,选择一种有效的技术并对临床发现做出准确的解释对于 22q11.2DS 患者的诊断至关重要。本系统性综述提供了过去 20 年来对 22q11.2DS 先天性心脏病患者的最新研究情况以及每次诊断背后的调查过程。我们在 PubMed、Embase 和 LILACS 中使用迪乔治综合征、先天性心脏病和细胞遗传学分析的所有词条进行了检索。经过筛选,60 篇论文符合审稿条件。我们提出了一个新观点,即室间隔缺损可能是 22q11.2DS 患者的关键心脏发现。此外,我们还介绍了分子技术和心脏评估作为有价值的工具,以指导研究人员今后的研究工作。
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引用次数: 0
Parents' Supernatural Beliefs on Causes of Birth Defects: A Review from Islamic Perspective. 父母对出生缺陷原因的超自然信仰:从伊斯兰教的角度回顾
IF 0.4 Q4 PEDIATRICS Pub Date : 2023-02-08 eCollection Date: 2023-06-01 DOI: 10.1055/s-0043-1761268
Hüseyin Çaksen

In this article, parents' supernatural beliefs on causes of birth defects were reviewed and discussed from Islamic perspective to draw attention to the importance of supernatural powers in Islamic teachings. Birth defects have been known since ancient ages and many people with different birth defects, who lived in antiquity, have been described. Although reasons for birth defects given in early medieval, 13th, 16th, and 21st centuries medical texts showed differences, numerous people in different cultures of the world have believed the effects of supernatural powers can cause birth defects since early medieval ages. Sixteenth century medical authors associated biomedical explanations with social upheavals and theology in order to understand the individual sins and the signs of the times presented by Allah through malformed human births. However, there is no religious phrase mentioning about causes of birth defects in medical textbooks of the 21st century. Based on the Islamic teachings, we would like to emphasize that supernatural beliefs including "Allah's will and qadar," "a test from Allah," "a punishment from Allah," "nazar (evil eye)," "sihr (magic or sorcery)," and "jinn possession" believed by parents as a cause of birth defects are right, real, and true, and not superstition or misconception. The Quran says "everything is determined by Almighty Allah" and "no kind of calamity can occur, except by the leave of Allah." So, we strongly believe that religious teachings must be integrated into modern medicine. The need for religion is not only for Muslims but also for all people a need of pre-eternity and posteternity. The unfortunate humanity today suffers in great pain from the constant sorrow and disasters of being deprived of the religion blessing.

本文从伊斯兰教的角度回顾和讨论了父母对出生缺陷原因的超自然信仰,以引起人们对超自然力量在伊斯兰教义中的重要性的关注。自古以来,人们就知道出生缺陷的存在,并对古代许多患有不同出生缺陷的人进行了描述。虽然中世纪早期、13 世纪、16 世纪和 21 世纪的医学文献中关于出生缺陷的原因存在差异,但自中世纪早期以来,世界上不同文化背景下的许多人都相信超自然力量的影响会导致出生缺陷。16 世纪的医学作者将生物医学解释与社会动荡和神学联系在一起,以理解个人的罪孽和安拉通过畸形人的出生所展现的时代征兆。然而,在 21 世纪的医学教科书中,没有任何宗教用语提及出生缺陷的原因。基于伊斯兰教义,我们要强调的是,父母们认为的导致出生缺陷的超自然信仰,包括 "安拉的旨意和卡达尔"、"安拉的考验"、"安拉的惩罚"、"邪眼"、"魔法或巫术"、"精灵附体 "等,都是正确的、真实的、真实的,而不是迷信或误解。古兰经》说:"一切都是全能的真主所决定的","除非真主许可,否则任何灾难都不能发生"。因此,我们坚信,宗教教义必须融入现代医学。对宗教的需求不仅是穆斯林的需求,也是所有人的需求,是前现代和后现代的需求。今天,不幸的人类因得不到宗教的庇佑而不断遭受悲伤和灾难,承受着巨大的痛苦。
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引用次数: 0
Contributing Reviewers in 2022. 2022 年的特约评审员。
IF 0.4 Pub Date : 2023-01-18 eCollection Date: 2023-03-01 DOI: 10.1055/s-0043-1761176
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引用次数: 0
Importance of Religious Coping in Bereaved Parents after the Death of a Child with Genetic Disorder. 遗传病患儿死亡后,宗教应对对丧亲者的重要性。
IF 0.4 Q4 PEDIATRICS Pub Date : 2022-12-07 eCollection Date: 2023-06-01 DOI: 10.1055/s-0042-1759781
Hüseyin Çaksen
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引用次数: 0
A Rare Biotinidase Deficiency in the Pediatrics Population: Genotype-Phenotype Analysis. 儿科人群中罕见的生物素酶缺乏症:基因型表型分析。
IF 0.4 Pub Date : 2022-11-01 eCollection Date: 2023-03-01 DOI: 10.1055/s-0042-1757887
Balachander Kannan, Hepzibah Kirubamani Navamani, Vijayashree Priyadharsini Jayaseelan, Paramasivam Arumugam

Biotinidase (BTD) deficiency is a rare autosomal recessive metabolic disorder caused by insufficient biotin metabolism, where it cannot recycle the vitamin biotin. When this deficiency is not treated with supplements, it can lead to severe neurological conditions. Approximately 1 in 60,000 newborns are affected by BTD deficiency. The BTD deficiency causes late-onset biotin-responsive multiple carboxylase deficiency, which leads to acidosis or lactic acidosis, hypoglycemia, and abnormal catabolism. BTD deficiency is of two types based on the amount of BTD Enzyme present in the serum. A wide range of pathogenic mutations in the BTD gene are reported worldwide. Mutations in the BTD gene lead to profound and partial BTD deficiency. Profound BTD deficiency results in a severe pathogenic condition. A high frequency of newborns are affected with the partial deficiency worldwide. They are mostly asymptomatic, but symptoms may appear during stressful conditions such as fasting or viral infections. Several pathogenic mutations are significantly associated with neurological, ophthalmological, and skin problems along with several other clinical features. This review discusses the BTD gene mutation in multiple populations detected with phenotypic features. The molecular-based biomarker screening is necessary for the disease during pregnancy, as it could be helpful for the early identification of BTD deficiency, providing a better treatment strategy. Moreover, implementing newborn screening for the BTD deficiency helps patients prevent several diseases.

生物素酶(BTD)缺乏症是一种罕见的常染色体隐性代谢障碍,由生物素代谢不足引起,无法回收维生素-生物素。如果不使用补充剂治疗这种缺陷,可能会导致严重的神经系统疾病。大约每60000名新生儿中就有1人患有BTD缺乏症。BTD缺乏会导致晚发型生物素反应性多羧化酶缺乏,从而导致酸中毒或乳酸酸中毒、低血糖和异常分解代谢。基于血清中存在的BTD酶的量,BTD缺乏有两种类型。BTD基因的致病性突变在世界范围内都有报道。BTD基因突变导致BTD严重和部分缺乏。严重的BTD缺乏会导致严重的致病性疾病。在全世界范围内,高频率的新生儿受到部分缺乏症的影响。他们大多没有症状,但在禁食或病毒感染等压力条件下可能会出现症状。一些致病性突变与神经、眼科和皮肤问题以及其他一些临床特征显著相关。这篇综述讨论了BTD基因突变在多个群体中检测到的表型特征。基于分子的生物标志物筛查对于妊娠期间的疾病是必要的,因为它可能有助于早期识别BTD缺乏症,提供更好的治疗策略。此外,实施新生儿BTD缺乏症筛查有助于患者预防多种疾病。
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引用次数: 1
Revisiting Exome Data Identified Missed Splice Site Variant of the Asparagine Synthetase ( ASNS ) Gene. 重新审视外显子组数据发现天冬酰胺合成酶(ASNS)基因缺失剪接位点变异
IF 0.4 Q4 PEDIATRICS Pub Date : 2022-10-13 eCollection Date: 2024-03-01 DOI: 10.1055/s-0042-1757193
Ghalia Al-Kasbi, Fathiya Al-Murshedi, Amna Al-Futaisi, Tariq Al-Jabry, Fahad Zadjali, Said Al-Yahyaee, Almundher Al-Maawali

Next-generation sequencing, such as whole-exome sequencing (WES), is increasingly used in the study of Mendelian disorders, yet many are reported as "negative." Inappropriate variant annotation and filtering steps are reasons for missing the molecular diagnosis. Noncoding variants, including splicing mutations, are examples of variants that can be overlooked. Herein, we report a family of four affected newborns, and all presented with severe congenital microcephaly. Initial research WES analysis identified a damaging homozygous variant in NME1 gene as a possible cause of primary microcephaly phenotype in these patients. However, reanalysis of the exome data uncovered a biallelic splice site variant in asparagine synthetase gene which seems to be the possible cause of the phenotype in these patients. This study highlights the importance of revisiting the exome data and the issue of "negative" exome and the afterward approaches to identify and prove new candidate genes.

全外显子组测序(WES)等下一代测序技术越来越多地用于孟德尔疾病的研究,但许多测序结果被报告为 "阴性"。不恰当的变异注释和过滤步骤是导致分子诊断漏诊的原因。非编码变异(包括剪接突变)就是容易被忽视的变异。在此,我们报告了一个由四名受影响的新生儿组成的家庭,他们都患有严重的先天性小头畸形。初步研究的 WES 分析发现,NME1 基因中的一个破坏性同源变异可能是导致这些患者出现原发性小头畸形表型的原因。然而,对外显子组数据的重新分析发现了天冬酰胺合成酶基因的一个双重复剪接位点变异,该变异似乎是导致这些患者出现表型的可能原因。这项研究强调了重新研究外显子组数据和 "阴性 "外显子组问题的重要性,以及之后识别和证明新候选基因的方法。
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引用次数: 0
Impact of Deletion on Angelman Syndrome Phenotype Variability: Phenotype-Genotype Correlation in 97 Patients with Motor Developmental Delay. 基因缺失对安吉尔曼综合征表型变异的影响:97例运动发育迟缓患者的表型-基因型相关性。
IF 0.4 Pub Date : 2022-08-16 eCollection Date: 2024-03-01 DOI: 10.1055/s-0042-1751268
Hanae Daha Belghiti, Meriame Abbassi, Hanane Sayel, Mohamed Ahakoud, Badr Eddine El Makhzen, Norman Lee, Silvia Russo, Sana Chaouki, Laila Bouguenouch

Angelman syndrome (AS) is a rare neurodevelopmental disorder due to genetic defects involving chromosome 15, known by intellectual disability, cognitive and behavioral disorders, ataxia, delayed motor development, and seizures. This study highlights the clinical spectrum and molecular research to establish the genotype-phenotype correlation in the pediatric Moroccan population. Methylation-specific-polymerase chain reaction (MS-PCR) is a primordial technique not only to identify the genetic mechanism of AS but also to characterize the different molecular classes induced in the appearance of the clinical symptoms. Patients with positive methylation profile were additionally studied by fluorescent in situ hybridization. Sequencing analysis of the UBE3A gene was performed for patients with negative MS-PCR. We used Fisher's test to assess differences in the distribution of features frequencies among the deletional and the nondeletional group. Statistical analysis was performed using R project. We identified from 97 patients diagnosed with AS, 14 (2.06%) had a classical AS phenotype, while 70 (84.5%) patients displayed a subset of consistent and frequent criteria. Development delay was shown severe in 63% and moderate in 37%. Nineteen out of 97 of them had MS-PCR positive in which 17 (89.47%) had 15q11-q13 deletion. Deletion patients presented a higher incidence of epileptic seizures ( p  = 0.04), ataxia ( p  = 0.0008), and abnormal electroencephalogram (EEG) profile ( p  = 0.003). We further found out a frameshift deletion located at exon 9 of the UBE3A gene discovered in a 5 years old patient. We report in this study the genotype-phenotype correlation using different molecular testing. Correlation analysis did not reveal any statistical differences in phenotypic dissimilarity between deletion and nondeletion groups for most clinical features, except the correlation was highly significant in the abnormal EEG. According to our findings, we recommend offering MS-PCR analysis to all patients with severe intellectual disability, developmental delay, speech impairment, happy demeanor, and hypopigmentation.

安杰尔曼综合征(AS)是一种罕见的神经发育障碍性疾病,由涉及 15 号染色体的遗传缺陷引起,以智力障碍、认知和行为障碍、共济失调、运动发育迟缓和癫痫发作而闻名。本研究强调了摩洛哥儿科人群的临床谱系和分子研究,以确定基因型与表型之间的相关性。甲基化特异性聚合酶链反应(MS-PCR)是一项基本技术,不仅能确定强直性脊柱炎的遗传机制,还能描述临床症状出现时诱发的不同分子类别。此外,还通过荧光原位杂交对甲基化谱呈阳性的患者进行了研究。对 MS-PCR 阴性的患者进行了 UBE3A 基因测序分析。我们使用费雪检验来评估缺失组和非缺失组之间特征频率分布的差异。统计分析使用 R 项目进行。我们从97名确诊为强直性脊柱炎的患者中发现,14名患者(2.06%)具有典型的强直性脊柱炎表型,而70名患者(84.5%)则显示了一组一致的常见标准。63%的患者表现为严重发育迟缓,37%为中度发育迟缓。97 例患者中有 19 例 MS-PCR 阳性,其中 17 例(89.47%)有 15q11-q13 缺失。缺失患者癫痫发作(p = 0.04)、共济失调(p = 0.0008)和脑电图(EEG)异常(p = 0.003)的发生率较高。我们还在一名 5 岁患者身上发现了 UBE3A 基因外显子 9 的缺失。我们在本研究中报告了使用不同分子检测方法的基因型与表型之间的相关性。相关性分析表明,在大多数临床特征方面,缺失组和非缺失组的表型差异没有统计学差异,但在异常脑电图方面相关性非常显著。根据我们的研究结果,我们建议对所有有严重智力障碍、发育迟缓、语言障碍、性格开朗和色素沉着的患者进行 MS-PCR 分析。
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引用次数: 0
Inborn Errors of Ketogenesis: Novel Variants, Clinical Presentation, and Follow-Up in a Series of Four Patients. 先天性生酮错误:四名患者的新变异、临床表现和随访。
IF 0.4 Pub Date : 2022-07-12 eCollection Date: 2024-03-01 DOI: 10.1055/s-0042-1749362
Haseena Sait, Somya Srivastava, Somesh Kumar, Bijo Varughese, Manmohan Pandey, Manjunath Venkatramaiah, Parul Chaudhary, Amita Moirangthem, Kausik Mandal, Seema Kapoor

Inborn errors of ketogenesis are rare disorders that result in acute and fulminant decompensation during lipolytic stress, particularly in infants and children. These include mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase (HMGCS) deficiency and HMG-CoA lyase (HMGCL) deficiency. In this series, we describe the clinical, biochemical, and molecular profiles of four patients along with dietary interventions and their outcomes on a long-term follow-up. Two patients each of HMGCS and HMGCL deficiency were evaluated with clinical history, biochemical investigations, including tandem mass spectrometry (TMS) and urine gas chromatography-mass spectrometry (GCMS). Molecular analysis was performed by whole-exome sequencing, as well as exon array validated by long-range polymerase chain reaction. All individuals were diagnosed with acute metabolic decompensation in the early infancy period except one with HMGCL deficiency who had the first presentation at 5 years of age. Central nervous system manifestations, severe metabolic acidosis, hyperammonemia, hypoglycemia with a normal lactate, and absence of urinary ketones were observed in all the affected individuals. The disorder was life-threatening in three individuals and one succumbed to the illness. TMS was nonspecific and urine GCMS revealed dicarboxylic aciduria in HMGCS deficiency. Both the patients with HMGCL deficiency demonstrated elevated 3 hydroxyisovaleryl carnitine levels in TMS and metabolites of leucine degradation in urine GCMS. We identified five novel variants that included a large deletion involving exon 2 in HMGCL gene. There was no evidence of long-term neurological sequelae in the living individuals. Diet with moderation of fat intake was followed in two individuals with HMGCS deficiency. Low leucine and protein diet with moderation of fat intake was followed in the individual with HMGCL deficiency. All affected individuals are thriving well with no further major metabolic decompensation.

先天性生酮错误是一种罕见的疾病,会在脂肪分解应激时导致急性和暴发性失代偿,尤其是在婴儿和儿童中。这些疾病包括线粒体 3-羟基-3-甲基戊二酰-CoA(HMG-CoA)合成酶(HMGCS)缺乏症和 HMG-CoA 裂解酶(HMGCL)缺乏症。在这个系列中,我们描述了四名患者的临床、生化和分子特征,以及饮食干预和长期随访的结果。我们对 HMGCS 和 HMGCL 缺乏症患者各两名进行了临床病史评估和生化检查,包括串联质谱法(TMS)和尿液气相色谱-质谱法(GCMS)。分子分析是通过全外显子组测序以及长程聚合酶链反应验证的外显子阵列进行的。除一名 HMGCL 缺乏症患者在 5 岁时首次发病外,所有患者均在婴儿期早期被诊断为急性代谢失调。所有患者都出现了中枢神经系统表现、严重的代谢性酸中毒、高氨血症、低血糖但乳酸正常以及尿酮体缺失。其中三人的病情危及生命,一人因病死亡。TMS 为非特异性,尿液 GCMS 显示 HMGCS 缺乏症患者有二羧酸尿症。两名 HMGCL 缺乏症患者的 TMS 和尿液 GCMS 均显示 3-羟基异戊酰基肉碱水平升高,尿液 GCMS 则显示亮氨酸降解代谢物升高。我们发现了五个新型变异体,其中包括涉及 HMGCL 基因第 2 外显子的大缺失。没有证据表明在世的个体会出现长期的神经系统后遗症。两名 HMGCS 缺乏症患者在饮食中摄入适量脂肪。HMGCL 缺乏症患者的饮食则以低亮氨酸和蛋白质为主,适量摄入脂肪。所有患者均恢复良好,没有再出现新陈代谢失调的情况。
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引用次数: 0
Pattern Recognition of Common Multiple Congenital Malformation Syndromes with Underlying Chromatinopathy. 常见多发性先天畸形综合征与潜在染色质病的模式识别。
IF 0.4 Pub Date : 2022-06-27 eCollection Date: 2024-03-01 DOI: 10.1055/s-0042-1748019
Anupriya Kaur, Chakshu Chaudhry, Parminder Kaur, Roshan Daniel, Priyanka Srivastava

Chromatinopathy is an emerging category of multiple malformation syndromes caused by disruption in global transcriptional regulation with imbalances in the chromatin states (i.e., open or closed chromatin). These syndromes are caused by pathogenic variants in genes coding for the writers, erasers, readers, and remodelers of the epigenetic machinery. Majority of these disorders (93%) show neurological dysfunction in the form of intellectual disability. Other overlapping features are growth abnormalities, limb deformities, and immune dysfunction. In this study, we describe a series of children with six common chromatinopathy syndromes with an aim to develop pattern recognition of this emerging category of multiple malformation syndromes.

染色质病是一种新出现的多发性畸形综合征,由染色质状态(即开放或封闭染色质)失衡导致的全局转录调控紊乱引起。这些综合征是由编码表观遗传机制的撰写者、擦除者、阅读者和重塑者的基因中的致病变异引起的。这些疾病中的大多数(93%)表现为智力障碍形式的神经功能障碍。其他重叠特征包括生长异常、肢体畸形和免疫功能障碍。在本研究中,我们描述了一系列患有六种常见染色质病综合征的儿童,旨在对这一新兴的多重畸形综合征类别进行模式识别。
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引用次数: 0
Ceroid Lipofuscinosis in Children: Author's Reply. 儿童Ceroid Lipofuscinosis:作者回复。
IF 0.4 Pub Date : 2022-06-01 DOI: 10.1055/s-0042-1748157
Vykuntaraju K Gowda
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引用次数: 0
期刊
Journal of pediatric genetics
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