Expanding the phenotype of GMPPB mutations

Mutations of GDP mannose pyrophosphorylase B (GMPPB) cause an early-onset muscular dystrophy and associated extra-muscular features. Cabrera-Serrano et al. broaden the clinical spectrum of this dystroglycanopathy by identifying patients with a milder phenotype presenting in adolescence or adulthood, including one with isolated episodes of rhabdomyolysis.Dystroglycanopathies are a heterogeneous group of diseases with a broad phenotypic spectrum ranging from severe disorders with congenital muscle weakness, eye and brain structural abnormalities and intellectual delay to adult-onset limb-girdle muscular dystrophies without mental retardation. Most frequently the disease onset is congenital or during childhood. The exception is FKRP mutations, in which adult onset is a common presentation. Here we report eight patients from five non-consanguineous families where next generation sequencing identified mutations in the GMPPB gene. Six patients presented as an adult or adolescent-onset limb-girdle muscular dystrophy, one presented with isolated episodes of rhabdomyolysis, and one as a congenital muscular dystrophy. This report expands the phenotypic spectrum of GMPPB mutations to include limb-girdle muscular dystrophies with adult onset with or without intellectual disability, or isolated rhabdomyolysis.