Expanding the Phenotype of B3GALNT2-Related Disorders

Dystroglycanopathies are a group of congenital muscular dystrophies (CMDs) that include a broad phenotypic spectrum ranging from late-onset limb-girdle muscular dystrophy to severe muscle-eye-brain disease, Walker-Warburg syndrome, and Fukuyama congenital muscular dystrophy. In addition to clinical heterogeneity, CMDs are characterized by genetic heterogeneity. To date, 18 genes have been associated with CMDs. One of them is B3GALNT2, which encodes the beta-1,3-N-acetylgalactosaminyltransferase 2 that glycosylates alpha-dystroglycan. In this study, using exome sequencing, we identify a homozygous frameshift variant in B3GALNT2 due to a mixed uniparental disomy of chromosome 1 in a 7-year-old girl with global developmental delay, severely delayed active language development, and autism spectrum disorder but without any symptoms of muscular dystrophy. In addition to this case, we also provide an overview of all previously reported cases, further expanding the phenotypic spectrum.

Automated summary

Dystroglycanopathies are a group of congenital muscular dystrophies that show a wide range of phenotypes. They are not only clinically heterogeneous but also genetically heterogeneous. This study identifies a novel mutation in the B3GALNT2 gene associated with CMDs. Through a study on uniparental disomy, a unique case is discovered. Additionally, an overview of previously reported cases is provided, expanding the phenotypic spectrum.