Zhao Meifang, Liu Yuxing, Fan Liangliang, Liu Zhaochuan, Deng Yao, Tao Lihong
Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China.
Department of Cell Biology, School of Life Sciences, Central South University, Changsha, China.
J Cell Mol Med. 2025 Aug;29(15):e70667. doi: 10.1111/jcmm.70667.
Congenital muscular dystrophy (CMD) is a genetic muscle disorder characterised by muscle weakness and degeneration, either present at birth or emerging in middle age, often leading to progressive disability. MDC1A is a subtype of CMD caused by mutations in the LAMA2 gene. In this study, we investigated a family affected by CMD from a remote rural area. The proband exhibited typical muscle weakness symptoms, though with a delayed onset. By combining whole-exome sequencing with bioinformatics analysis, we explored the genetic aetiology of this family. A novel homozygous missense mutation (NM_000426: c.7412G>A; p.G2471D) of the LAMA2 gene was detected in the proband. The proband's parents were found to carry the heterozygous mutation. Bioinformatic analysis indicated that the amino acid residue is highly conserved and has low tolerance to variation, suggesting a high pathogenic potential of the mutation. Based on genetic analysis, the proband was subsequently diagnosed with MDC1A. In conclusion, a novel LAMA2 mutation was identified in a Chinese family with CMD. This discovery not only offers valuable insights for the patient's diagnosis and potential therapeutic strategies but also broadens the known spectrum of LAMA2 mutations.
先天性肌营养不良（CMD）是一种遗传性肌肉疾病，其特征为肌肉无力和退化，可在出生时就存在，也可在中年时出现，常导致进行性残疾。MDC1A是由LAMA2基因突变引起的CMD的一种亚型。在本研究中，我们调查了一个来自偏远农村地区的受CMD影响的家庭。先证者表现出典型的肌肉无力症状，不过发病较晚。通过将全外显子组测序与生物信息学分析相结合，我们探究了这个家庭的遗传病因。在先证者中检测到LAMA2基因的一个新的纯合错义突变（NM_000426: c.7412G>A；p.G2471D）。发现先证者的父母携带该杂合突变。生物信息学分析表明该氨基酸残基高度保守，对变异的耐受性低，提示该突变具有较高的致病潜力。基于遗传分析，先证者随后被诊断为MDC1A。总之，在一个患有CMD的中国家庭中鉴定出一个新的LAMA2突变。这一发现不仅为患者的诊断和潜在治疗策略提供了有价值的见解，也拓宽了已知的LAMA2突变谱。
