Mild limb girdle muscular dystrophy R9 phenotype caused by novel compound heterozygous FKRP gene mutation.

Ikhlass Belhassen, Rita Menassa, Salma Sakka, Laurence Michel-Calemard, Nathalie Streichenberger, Dorra Ben Ayed, Nadia Bouattour, Mariem Dammak, Chokri Mhiri
{"title":"Mild limb girdle muscular dystrophy R9 phenotype caused by novel compound heterozygous FKRP gene mutation.","authors":"Ikhlass Belhassen, Rita Menassa, Salma Sakka, Laurence Michel-Calemard, Nathalie Streichenberger, Dorra Ben Ayed, Nadia Bouattour, Mariem Dammak, Chokri Mhiri","doi":"10.36185/2532-1900-391","DOIUrl":null,"url":null,"abstract":"<p><p>Fukutin-related protein (FKRP) mutations cause a broad spectrum of muscular dystrophies, from a relatively mild limb-girdle muscular dystrophy type 9 (LGMDR9) to severe congenital muscular dystrophy (CMD). This study aims to report two siblings belonging to a non-consanguineous Tunisian family harboring a novel compound heterozygous <i>FKRP</i> variant and presenting a mild LGDMR9 phenotype. For mutation screening, massive parallel sequencing was performed, followed by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) to validate the existence of the discovered variants. The absence of alpha-dystroglycan was determined by immunohistochemistry. Brain and thigh magnetic resonance imaging (MRI) were performed to detect thigh and brain abnormalities. The two siblings had a late age at onset and clinical examination showed that the pelvic girdles had a predominantly proximal and symmetrical distribution of weakness without cardiac or respiratory involvement. They both had a modified Gardner-Medwin Walton Scale mGMWS grade of 4 and a modified Rankin Scale (mRS) score of 1. The DNA sequencing revealed a novel deletion of exons 2 and 3 in one allele and a missense mutation c.1364C > A, which has been reported to be responsible for congenital muscular dystrophy and mental retardation on the second allele. The simultaneous presence of the two variations in the two cases suggests that the variants segregate with the pathophysiology.</p>","PeriodicalId":93851,"journal":{"name":"Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology","volume":"42 4","pages":"106-112"},"PeriodicalIF":0.0000,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10883327/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.36185/2532-1900-391","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Fukutin-related protein (FKRP) mutations cause a broad spectrum of muscular dystrophies, from a relatively mild limb-girdle muscular dystrophy type 9 (LGMDR9) to severe congenital muscular dystrophy (CMD). This study aims to report two siblings belonging to a non-consanguineous Tunisian family harboring a novel compound heterozygous FKRP variant and presenting a mild LGDMR9 phenotype. For mutation screening, massive parallel sequencing was performed, followed by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) to validate the existence of the discovered variants. The absence of alpha-dystroglycan was determined by immunohistochemistry. Brain and thigh magnetic resonance imaging (MRI) were performed to detect thigh and brain abnormalities. The two siblings had a late age at onset and clinical examination showed that the pelvic girdles had a predominantly proximal and symmetrical distribution of weakness without cardiac or respiratory involvement. They both had a modified Gardner-Medwin Walton Scale mGMWS grade of 4 and a modified Rankin Scale (mRS) score of 1. The DNA sequencing revealed a novel deletion of exons 2 and 3 in one allele and a missense mutation c.1364C > A, which has been reported to be responsible for congenital muscular dystrophy and mental retardation on the second allele. The simultaneous presence of the two variations in the two cases suggests that the variants segregate with the pathophysiology.

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
新型复合杂合子 FKRP 基因突变导致轻度肢腰肌营养不良症 R9 表型。
福丁相关蛋白(FKRP)突变可导致多种肌肉萎缩症,从相对轻微的肢腰肌营养不良症9型(LGMDR9)到严重的先天性肌肉萎缩症(CMD)。本研究旨在报告一个突尼斯非血缘家族中的两对兄弟姐妹,他们携带一种新型复合杂合FKRP变异体,表现为轻度LGDMR9表型。为了筛选变异,研究人员进行了大规模平行测序,随后又进行了桑格测序和多重连接依赖性探针扩增(MLPA),以验证所发现变异的存在。通过免疫组化确定了α-肌张力蛋白的缺失。大脑和大腿磁共振成像(MRI)检测了大腿和大脑的异常。两兄妹的发病年龄较晚,临床检查显示,骨盆腰部的无力主要呈近端对称分布,没有心脏或呼吸系统受累。DNA测序结果显示,一个等位基因的第2和第3外显子发生了新的缺失,而第二个等位基因则发生了c.1364C > A的错义突变,据报道这种突变可导致先天性肌营养不良和智力低下。两个病例中同时出现这两种变异,表明变异与病理生理学存在分离。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
Abnormal expression of myosin heavy chains in early postnatal stages of spinal muscular atrophy type I at single fibre level. Efficacy of ephedrine treatment in COLQ-related Congenital Myasthenic Syndrome (CMS): longitudinal quantitative assessment in a 71-year-old man. Focal myositis: a literature review of clinical and immunopathological aspects. Gene therapy for Duchenne Muscular Dystrophy: assessing the readiness of Italian centres of expertise. The Epigenetic Rescue of Dystrophin Dysfunction study of givinostat in ambulatory Duchenne muscular dystrophy patients.
×
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