Dysferlinopathy in a cohort of Chinese patients: clinical features, mutation spectrum, and imaging findings.
Dysferlinopathy in a cohort of Chinese patients: clinical features, mutation spectrum, and imaging findings.
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中国患者的铁蛋白病队列：临床特征、突变谱和影像学表现
DOI：
10.1097/cm9.0000000000001343
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发表时间：
2021-02-08
影响因子：
6.1
通讯作者：
Lin F
中科院分区：
文献类型：
--
作者：
Guo QF;Ye ZX;Qiu LL;Lin X;Lai JH;Lin MT;Wang ZQ;Wang N;Lin F
编者按：DYSF基因突变会导致铁代谢障碍，这被称为一组常染色体隐性遗传的肌肉营养不良症。肌营养不良症包括Miyoshi肌病(MM)、肢带型肌营养不良症(LGMD2B)，以及其他非典型表型，如“近端-远端(PD)”表型和远端前室肌病。[1]目前，大多数患者的基因-表型相关性尚不清楚。此外，越来越多的非典型患者和临床表型的家族内变异性似乎使这种相关性变得复杂。在这里，我们结合了靶向下一代测序(NGS)和多重连接依赖的探针扩增基因测试，结合了一组卵巢功能障碍患者的大量临床数据。我们的目的是评估中国人群中特定突变的存在是否提供了详细的临床特征描述，估计了影响家庭内变异的因素，并获得了对表型-基因型相关性的新见解。该研究回顾了2014年7月至2019年2月期间在该院连续观察的来自23个家系的28名患者及其27名亲属。对大多数患者进行了血清肌酸激酶活性、肌电图、肌肉活检和肌肉磁共振成像(MRI)的评估。大腿和小腿肌肉的脂肪渗透通过增加信号强度来量化。[2]使用遗传性神经肌肉疾病(NMD)小组(Agilent Technologies，Santa Clara，CA，USA)对420个已知的NMD相关基因进行靶向NGS。经NGS筛选的突变经Sanger测序进一步证实。随后，根据美国医学遗传学和基因组学学院的标准和指南对所有新的变种进行了解释。所有涉及人体受试者的研究程序均符合机构委员会和/或国家研究委员会(福建医科大学附属第一医院，No.FYYY2006-01-19-01)和1964年的《赫尔辛基宣言》及其后来的修正案或类似的道德标准。研究中包括的所有个体参与者都获得了知情同意。
To the Editor: Mutations in the dysferlin (DYSF) gene lead to dysferlinopathy, which is referred to as a group of muscular dystrophies with autosomal recessive inheritance. Dysferlinopathy includes Miyoshi myopathy (MM), limb-girdle muscular dystrophy (LGMD2B), and other atypical phenotypes, such as the “proximo-distal (PD)” phenotype and distal anterior compartment myopathy.[1] Currently, the genotype-phenotype correlation in the majority of patients remains unclear. In addition, increasing cases of atypical patients and intra-familial variability of the clinical phenotype appear to complicate the correlation. Here, we combined targeted next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification genetic testing for dysferlinopathy with extensive clinical data in a cohort of patients with dysferlinopathy. We aimed to assess whether the existence of specific mutations in the Chinese population provides a detailed description of clinical features, estimate the factors influencing intra-familial variability, and obtain new insights into phenotype-genotype correlations.The study retrospectively observed 28 consecutive patients and their 27 relatives from 23 families between July 2014 and February 2019 in our hospital. Serum creatine kinase activity, electromyography, muscle biopsy, and muscle magnetic resonance imaging (MRI) were evaluated in the majority of patients. Fatty infiltration of the thigh and lower leg muscles was quantified by increased signal intensity as previously reported.[2] Targeted NGS was performed using an inherited neuromuscular disease (NMD) panel (Agilent Technologies, Santa Clara, CA, USA) of 420 known inherited NMD associated genes. The mutations screened by NGS were further confirmed by Sanger sequencing. All novel variants were subsequently interpreted according to the American College of Medical Genetics and Genomics standards and guidelines. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee and/or national research committee (The First Affiliated Hospital of Fujian Medical University, No. FYYY2006-01-19-01) and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.