Hu Chaoping, Shi Yiyun, Zhao Lei, Zhou Shuizhen, Wang Yi, Li Xihua, Yu Lifei
Children's Hospital of Fudan University, Shanghai, China.
Neurol Sci. 2025 Apr 7. doi: 10.1007/s10072-025-08124-8.
Collagen VI-related disorder (COL6-RD) is an inherited neuromuscular disease characterized by a broad spectrum of phenotypes.
Eight families with autosomal dominant COL6-RD were recruited. Clinical manifestations, laboratory findings, electrophysiological results, molecular analyses, and pathological outcomes of eight index patients and their affected family members were systematically collected and reviewed.
Pathogenic variants were identified in four families in the COL6A1 gene, one family in the COL6A2 gene, and three families in the COL6A3 gene. Among the index patients, three were classified as moderate progressive Ullrich congenital muscular dystrophy (UCMD), four exhibited mild UCMD or Bethlem myopathy, and one was diagnosed with Bethlem myopathy. The phenotypic presentation was relatively consistent within four families. However, intra-familial phenotypic variability was observed in four families, encompassing a wide range of onset ages, patterns and degrees of muscle weakness, rates of contracture progression, severity of skin changes, and age at loss of ambulation.
Inter- and intra-familial phenotypic variability is prevalent in autosomal dominant COL6-RDs. When predicting the clinical course and severity for patients, it is crucial to integrate a comprehensive set of information, including mutation sites and types, family history, and early presenting features.
胶原蛋白VI相关疾病（COL6-RD）是一种遗传性神经肌肉疾病，具有广泛的表型。
招募了8个常染色体显性COL6-RD家族。系统收集并回顾了8例索引患者及其受影响家庭成员的临床表现、实验室检查结果、电生理结果、分子分析和病理结果。
在COL6A1基因的4个家族、COL6A2基因的1个家族和COL6A3基因的3个家族中鉴定出致病变异。在索引患者中，3例被归类为中度进行性乌尔里希先天性肌营养不良（UCMD），4例表现为轻度UCMD或贝斯勒姆肌病，1例被诊断为贝斯勒姆肌病。4个家族中的表型表现相对一致。然而，在4个家族中观察到家族内表型变异性，包括广泛的发病年龄、肌肉无力的模式和程度、挛缩进展率、皮肤变化的严重程度以及失去行走能力的年龄。
常染色体显性COL6-RD中家族间和家族内表型变异性普遍存在。在预测患者的临床病程和严重程度时,整合包括突变位点和类型、家族史以及早期表现特征在内的全面信息至关重要。
