Collagen VI related myopathy: Clinical variability of triple helical domain mutations of COL6A mutations

Abstract

Background and Purpose: Mutations in collagen VI-related genes (COL6A1, COL6A2, andCOL6A3) cause Ullrich congenital muscular dystrophy (UCMD) the severe disease, the mild Bethlem myopathy (BM) and the intermediate phenotype. These were not separate entities but represent a continuous clinical spectrum. We aimed to analyze the clinical, pathologic, and genetic characteristics of patients with collagen VI-related myopathy in Hong Kong. Methods: We reviewed the clinical, pathologic, radiological and genetic features in 8 patients with collagenVI-related myopathy from 8 families, with confirmed mutations of collagen VI-related genes. Results: One patient showed the phenotype of typical UCMD, 3 patients had the intermediate collagen VI-related myopathies (IM), and 4 patients had the BM phenotype. Based on genetic analysis, all patients had mutation in the triple-helical domain of the COL6A related genes. The mutations affected either in COL6A1, COL6A2, COL6A3 gene and include 8 point mutations, one inframe deletion and one splice site insertion. Dominant negative mutations occur in 6 patients and recessive mutations mainly in 2 patients with BM phenotype. Additionally, we found two novel mutations: NM_001849.3: c.1084_1092del, p.(Ser362_Gly364del)] and NM_001849.3: c.811G>C, p.(Gly271Arg) in COL6A2 Conclusions: Missense mutations in the triple-helical domain of the three major collagen VI genes are the most common mutations related to collagen VI-related myopathy in Hong Kong. Mutations in the triple-helical domain of our patients give rise to a broad clinical spectrum from the mild end to the severe phenotype.