[P3-132] Phenotype/genotype analysis of collagen VI-related myopathy in a Chinese cohort
[Background]: Collagen VI-related myopathy represents a clinical continuum from Ullrich congenital muscular dystrophy (UCMD) to Bethlem myopathy (BM). We analyzed the clinical, pathological and genetic characteristics of 48 Chinese patients.
[Methods]: Clinical data were collected and muscle biopsies of some patients were analyzed. COL6A1, COL6A2 and COL6A3 exons were analyzed by direct sequencing or next generation sequencing (NGS). Mosaicism was detected by personal genome machine amplicon deep sequencing for mosaicism (PASM).
[Results]: Thirty-one were diagnosed as UCMD, with early onset and severe muscle weakness, striking distal joints hypermobility with proximal joints contractures and skin changes. Seventeen were diagnosed as BM, with relatively late onset, mild joint contractures and distal hyperlaxity and proximal muscle weakness. Muscle biopsies revealed dystrophic changes and immunohistochemical/immunofluorescence studies showed reduced levels of collagen VI at the muscle basement membrane and/or mislocalization in interstitial and perivascular regions. We identified 54 allelic mutations in COL6A1 (42.6%), COL6A2 (37.0%) and COL6A3 (20.4%). Among them, 34 were de novo, one was paternally and seven maternally dominantly inherited and twelve were autosomal recessive with 44 locating in the triple helical domain (THD). We found one case of somatic mutation in a parent by gDNA sequence chromatograms. The validation of mosaicism by PASM indicated a lower proportion of mutant allele.
[Conclusions]: Mutations we identified underscore importance of THD in the assembly and function of collagen VI. NGS is a valuable approach for diagnosis and provides useful information for genetic counseling.
[Methods]: Clinical data were collected and muscle biopsies of some patients were analyzed. COL6A1, COL6A2 and COL6A3 exons were analyzed by direct sequencing or next generation sequencing (NGS). Mosaicism was detected by personal genome machine amplicon deep sequencing for mosaicism (PASM).
[Results]: Thirty-one were diagnosed as UCMD, with early onset and severe muscle weakness, striking distal joints hypermobility with proximal joints contractures and skin changes. Seventeen were diagnosed as BM, with relatively late onset, mild joint contractures and distal hyperlaxity and proximal muscle weakness. Muscle biopsies revealed dystrophic changes and immunohistochemical/immunofluorescence studies showed reduced levels of collagen VI at the muscle basement membrane and/or mislocalization in interstitial and perivascular regions. We identified 54 allelic mutations in COL6A1 (42.6%), COL6A2 (37.0%) and COL6A3 (20.4%). Among them, 34 were de novo, one was paternally and seven maternally dominantly inherited and twelve were autosomal recessive with 44 locating in the triple helical domain (THD). We found one case of somatic mutation in a parent by gDNA sequence chromatograms. The validation of mosaicism by PASM indicated a lower proportion of mutant allele.
[Conclusions]: Mutations we identified underscore importance of THD in the assembly and function of collagen VI. NGS is a valuable approach for diagnosis and provides useful information for genetic counseling.