Lee Jung Hwan, Shin Ha Young, Park Hyung Jun, Kim Se Hoon, Kim Seung Min, Choi Young Chul
Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
Rehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, Seoul, Korea.
J Clin Neurol. 2017 Oct;13(4):331-339. doi: 10.3988/jcn.2017.13.4.331. Epub 2017 Aug 1.
Mutations in collagen VI-related genes (COL6A1, COL6A2, and COL6A3) cause Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD). These were previously believed to be separate disease entities, but they are now both classified as collagen VI-related myopathies, which cover a broad clinical spectrum. We aimed to analyze the clinical, pathologic, and genetic characteristics of patients with collagen VI-related myopathy in Korea.
We reviewed the clinical, pathologic, and genetic features in 22 patients with collagen VI-related myopathy from 13 families, as confirmed by genetic analysis of collagen VI-related genes.
The mean ages of the 22 patients at first symptom presentation and diagnosis were 4.5 and 24.9 years, respectively. Four patients in 4 families showed the phenotype of intermediate collagen VI-related myopathies (IM), 16 patients in 7 families had the BM phenotype, and 2 patients in 2 families presented with the typical UCMD phenotype. Based on genetic analysis, five patients (five families) comprising four with IM and one with typical UCMD had missense mutations in the triple-helical domain of COL6A1, and ten patients (four families) with BM showed exon-14-skipping mutations. Additionally, we found two novel mutations: c.956A>G (p.K319R) in COL6A1 and c.6221G>T (p.G2074V) in COL6A3.
Missense mutations in the triple-helical domain of COL6A1 are the most common mutations related to collagen VI-related myopathy in Korea. Patients with these mutations have a tendency toward an earlier disease onset and more severe progression compared to patients with other mutations.
胶原蛋白VI相关基因（COL6A1、COL6A2和COL6A3）的突变会导致贝斯勒肌病（BM）和乌尔里希先天性肌营养不良（UCMD）。这些疾病以前被认为是不同的疾病实体，但现在它们都被归类为胶原蛋白VI相关肌病，其涵盖了广泛的临床谱。我们旨在分析韩国胶原蛋白VI相关肌病患者的临床、病理和遗传特征。
我们回顾了13个家族中22例经胶原蛋白VI相关基因遗传分析确诊的胶原蛋白VI相关肌病患者的临床、病理和遗传特征。
22例患者首次出现症状和诊断时的平均年龄分别为4.5岁和24.9岁。4个家族中的4例患者表现为中间型胶原蛋白VI相关肌病（IM）的表型，7个家族中的16例患者具有BM表型，2个家族中的2例患者表现为典型的UCMD表型。基于遗传分析，5例患者（5个家族）包括4例IM患者和1例典型UCMD患者在COL6A1的三螺旋结构域有错义突变，10例BM患者（4个家族）显示外显子14跳跃突变。此外，我们发现了两个新突变：COL6A1中的c.956A>G（p.K319R）和COL6A3中的c.6221G>T（p.G2074V）。
COL6A1三螺旋结构域的错义突变是韩国与胶原蛋白VI相关肌病相关的最常见突变。与其他突变患者相比，这些突变患者有疾病发病更早、进展更严重的倾向。
