CONICET | Buscador de Institutos y Recursos Humanos

REPORT OF A BETHLEM MYOPATHY CASE ASSOCIATED WITH COL6A3 Carmen Llames Massini 1,2, Micaela Carcione 1,2, Chiara Mazzanti 1,2, Leonela Luce 1,2, Triana Visconti1,2, Macarena Bollana1,2, Florencia Giliberto1,2.1 Laboratorio de Distrofinopatías, Cátedra de Genética, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.2 Instituto de Inmunología, Genética y Metabolismo (INIGEM), CONICET - Universidad de Buenos Aires, Buenos Aires, Argentina.Muscular dystrophies (MD) are a group of rare inherited diseases that cause weakness and progressive degeneration of skeletal muscle. Since the clinical symptoms of MD overlap, it is important to carry out molecular studies to obtain a differential diagnosis and thus establish the standard of care. We describe the case of a mother and two children with symptoms consistent with hereditary myopathy, characterized by waist weakness and keloid scarring. The present work aims to identify the genetic alteration associated with this clinical picture. Whole exome sequencing (WES), variant screening, Sanger sequencing, and intrafamilial segregation of candidate variants were performed. From WES, a variant was found in COL6A3, whose alterations are associated with autosomal dominant and recessive inheritance of Limb-girdle MD. A missense variant NM_004369.3:c.6185G>A was identified in COL6A3, reported 2 times in LOVD3, classified as pathogenic, and absent in gnomAD. In addition, bioinformatic predictors determined a deleterious effect. Intrafamilial segregation identified the variant in the 3 individuals studied consistent with an autosomal dominant mode of inheritance. In conclusion, the detailed evidence allowed the COL6A3 variant to be associated with family symptoms. This work highlights the importance of using predictive programs and databases in conjunction with segregation studies to reach an accurate diagnosis.