Detection of somatic and germline mosaicism for the LAMP2 gene mutation c.808dupG in a Chinese family with Danon disease

Abstract Danon disease is a rare X-linked lysosomal storage disease characterized by hypertrophic cardiomyopathy, myopathy and mental retardation, and is due to a primary defect in lysosome-associated membrane protein-2 (LAMP 2). More than 26 mutations in the LAMP2 gene have been described, including a small number of de novo mutations, some of which are suspected to be caused by germline mosaicism. Here, we describe the first molecularly documented evidence of somatic mosaicism for a LAMP2 mutation, identified in the asymptomatic mother of a boy with Danon disease caused by the frameshift mutation c.808dupG (p.A270Gfx3) within exon 6. In addition, in order to gain insight into the possible explanation for the mother's lack of phenotype, the level of somatic mosaicism and the X-chromosome inactivation pattern were investigated. This study provides new insight into the causes of phenotypic variability in female mutation-carriers and underlines the importance of parental molecular testing for accurate genetic counseling for Danon disease.