KBTBD13 基因中的一个可能致病的变异体:三例内膜肌病 6 型患者的病例系列。

IF 3.2 4区 医学 Q2 CLINICAL NEUROLOGY Journal of neuromuscular diseases Pub Date : 2024-09-04 DOI:10.3233/JND-230196
Esmee S B van Kleef, Karlijn Bouman, Joery P F Molenaar, Josine M de Winter, Floor A M Duijkers, Filip Eftimov, Corien C Verschuuren-Bemelmans, Tineke van der Laan, Benno Küsters, Edoardo Malfatti, Erik-Jan Kamsteeg, Baziel G M van Engelen, Coen A C Ottenheijm, Jonne Doorduin, Nicol C Voermans
{"title":"KBTBD13 基因中的一个可能致病的变异体:三例内膜肌病 6 型患者的病例系列。","authors":"Esmee S B van Kleef, Karlijn Bouman, Joery P F Molenaar, Josine M de Winter, Floor A M Duijkers, Filip Eftimov, Corien C Verschuuren-Bemelmans, Tineke van der Laan, Benno Küsters, Edoardo Malfatti, Erik-Jan Kamsteeg, Baziel G M van Engelen, Coen A C Ottenheijm, Jonne Doorduin, Nicol C Voermans","doi":"10.3233/JND-230196","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Nemaline myopathy type 6 (NEM6) or KBTBD13-related congenital myopathy is the most prevalent type of nemaline myopathy in the Netherlands and is characterised by mild childhood-onset axial, proximal and distal muscle weakness with prominent neck flexor weakness combined with slowness of movements. The most prevalent variant in the Netherlands is the c.1222C > T p.(Arg408Cys) variant in the KBTBD13 gene, also called the Dutch founder variant.</p><p><strong>Objective: </strong>To provide a comprehensive clinical and functional characterisation of three patients to assess the pathogenicity of a newly identified variant in the KBTBD13 gene.</p><p><strong>Results: </strong>We present three cases (Patient 1: female, 76 years old; Patient 2: male, 63 years old; and his brother Patient 3: male, 61 years old) with a c.1222C > A p.(Arg408Ser) variant in the KBTBD13 gene. Patient 1 was also included previously in a histopathological study on NEM6. Symptoms of muscle weakness started in childhood and progressed to impaired functional abilities in adulthood. All three patients reported slowness of movements. On examination, they have mild axial, proximal and distal muscle weakness. None of the patients exhibited cardiac abnormalities. Spirometry in two patients showed a restrictive lung pattern. Muscle ultrasound showed symmetrically increased echogenicity indicating fatty replacement and fibrosis in a subset of muscles and histopathological analyses revealed nemaline rods and cores. Slower muscle relaxation kinetics with in vivo functional tests was observed. This was confirmed by in vitro functional tests showing impaired relaxation kinetics in isolated muscle fibres. We found a genealogic link between patient 1, and patient 2 and 3 nine generations earlier.</p><p><strong>Conclusions: </strong>The c.1222C > A p.(Arg408Ser) variant in the KBTBD13 gene is a likely pathogenic variant causing NEM6.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Likely Pathogenic variant in the KBTBD13 Gene: A Case Series of Three Patients with Nemaline Myopathy Type 6.\",\"authors\":\"Esmee S B van Kleef, Karlijn Bouman, Joery P F Molenaar, Josine M de Winter, Floor A M Duijkers, Filip Eftimov, Corien C Verschuuren-Bemelmans, Tineke van der Laan, Benno Küsters, Edoardo Malfatti, Erik-Jan Kamsteeg, Baziel G M van Engelen, Coen A C Ottenheijm, Jonne Doorduin, Nicol C Voermans\",\"doi\":\"10.3233/JND-230196\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Nemaline myopathy type 6 (NEM6) or KBTBD13-related congenital myopathy is the most prevalent type of nemaline myopathy in the Netherlands and is characterised by mild childhood-onset axial, proximal and distal muscle weakness with prominent neck flexor weakness combined with slowness of movements. The most prevalent variant in the Netherlands is the c.1222C > T p.(Arg408Cys) variant in the KBTBD13 gene, also called the Dutch founder variant.</p><p><strong>Objective: </strong>To provide a comprehensive clinical and functional characterisation of three patients to assess the pathogenicity of a newly identified variant in the KBTBD13 gene.</p><p><strong>Results: </strong>We present three cases (Patient 1: female, 76 years old; Patient 2: male, 63 years old; and his brother Patient 3: male, 61 years old) with a c.1222C > A p.(Arg408Ser) variant in the KBTBD13 gene. Patient 1 was also included previously in a histopathological study on NEM6. Symptoms of muscle weakness started in childhood and progressed to impaired functional abilities in adulthood. All three patients reported slowness of movements. On examination, they have mild axial, proximal and distal muscle weakness. None of the patients exhibited cardiac abnormalities. Spirometry in two patients showed a restrictive lung pattern. Muscle ultrasound showed symmetrically increased echogenicity indicating fatty replacement and fibrosis in a subset of muscles and histopathological analyses revealed nemaline rods and cores. Slower muscle relaxation kinetics with in vivo functional tests was observed. This was confirmed by in vitro functional tests showing impaired relaxation kinetics in isolated muscle fibres. We found a genealogic link between patient 1, and patient 2 and 3 nine generations earlier.</p><p><strong>Conclusions: </strong>The c.1222C > A p.(Arg408Ser) variant in the KBTBD13 gene is a likely pathogenic variant causing NEM6.</p>\",\"PeriodicalId\":16536,\"journal\":{\"name\":\"Journal of neuromuscular diseases\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-09-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of neuromuscular diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3233/JND-230196\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of neuromuscular diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3233/JND-230196","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景:6型神经性肌病(NEM6)或KBTBD13相关先天性肌病是荷兰最常见的神经性肌病类型,其特征是儿童期发病的轻度轴向、近端和远端肌无力,颈屈肌无力突出,伴有动作迟缓。荷兰最常见的变异是 KBTBD13 基因中的 c.1222C > T p.(Arg408Cys)变异,也称为荷兰始祖变异:目的:对三名患者的临床和功能特征进行全面分析,以评估新发现的 KBTBD13 基因变异体的致病性:结果:我们发现三例患者(患者1:女,76岁;患者2:男,63岁;患者3:男,61岁)的KBTBD13基因中存在c.1222C > A p.(Arg408Ser)变异。患者 1 之前还参加过一项关于 NEM6 的组织病理学研究。肌无力症状始于儿童时期,成年后逐渐发展为功能受损。三位患者均表示行动迟缓。经检查,他们有轻微的轴向、近端和远端肌无力。三位患者均无心脏异常。两名患者的肺活量检查显示肺部呈限制型。肌肉超声波显示对称性回声增高,表明部分肌肉中存在脂肪替代和纤维化,组织病理学分析显示有神经纤维棒和核心。在体内功能测试中观察到肌肉松弛动力学减慢。体外功能测试也证实了这一点,显示离体肌纤维的松弛动力学受损。我们发现患者 1 与九代之前的患者 2 和 3 之间存在谱系联系:结论:KBTBD13 基因中的 c.1222C > A p.(Arg408Ser) 变异很可能是导致 NEM6 的致病变异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
A Likely Pathogenic variant in the KBTBD13 Gene: A Case Series of Three Patients with Nemaline Myopathy Type 6.

Background: Nemaline myopathy type 6 (NEM6) or KBTBD13-related congenital myopathy is the most prevalent type of nemaline myopathy in the Netherlands and is characterised by mild childhood-onset axial, proximal and distal muscle weakness with prominent neck flexor weakness combined with slowness of movements. The most prevalent variant in the Netherlands is the c.1222C > T p.(Arg408Cys) variant in the KBTBD13 gene, also called the Dutch founder variant.

Objective: To provide a comprehensive clinical and functional characterisation of three patients to assess the pathogenicity of a newly identified variant in the KBTBD13 gene.

Results: We present three cases (Patient 1: female, 76 years old; Patient 2: male, 63 years old; and his brother Patient 3: male, 61 years old) with a c.1222C > A p.(Arg408Ser) variant in the KBTBD13 gene. Patient 1 was also included previously in a histopathological study on NEM6. Symptoms of muscle weakness started in childhood and progressed to impaired functional abilities in adulthood. All three patients reported slowness of movements. On examination, they have mild axial, proximal and distal muscle weakness. None of the patients exhibited cardiac abnormalities. Spirometry in two patients showed a restrictive lung pattern. Muscle ultrasound showed symmetrically increased echogenicity indicating fatty replacement and fibrosis in a subset of muscles and histopathological analyses revealed nemaline rods and cores. Slower muscle relaxation kinetics with in vivo functional tests was observed. This was confirmed by in vitro functional tests showing impaired relaxation kinetics in isolated muscle fibres. We found a genealogic link between patient 1, and patient 2 and 3 nine generations earlier.

Conclusions: The c.1222C > A p.(Arg408Ser) variant in the KBTBD13 gene is a likely pathogenic variant causing NEM6.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of neuromuscular diseases
Journal of neuromuscular diseases Medicine-Neurology (clinical)
CiteScore
5.10
自引率
6.10%
发文量
102
期刊介绍: The Journal of Neuromuscular Diseases aims to facilitate progress in understanding the molecular genetics/correlates, pathogenesis, pharmacology, diagnosis and treatment of acquired and genetic neuromuscular diseases (including muscular dystrophy, myasthenia gravis, spinal muscular atrophy, neuropathies, myopathies, myotonias and myositis). The journal publishes research reports, reviews, short communications, letters-to-the-editor, and will consider research that has negative findings. The journal is dedicated to providing an open forum for original research in basic science, translational and clinical research that will improve our fundamental understanding and lead to effective treatments of neuromuscular diseases.
期刊最新文献
A Likely Pathogenic variant in the KBTBD13 Gene: A Case Series of Three Patients with Nemaline Myopathy Type 6. An International Retrospective Early Natural History Study of LAMA2-Related Dystrophies. Life Expectancy and Causes of Death in Patients with Myotonic Dystrophy Type 2. E-Health & Innovation to Overcome Barriers in Neuromuscular Diseases. Report from the 3rd eNMD Congress: Pisa, Italy, 29-30 October 2021. Predictors of Loss of Ambulation in Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
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
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
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
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