B3GALNT2 is a gene associated with congenital muscular dystrophy with brain malformations

Congenital muscular dystrophies associated with brain malformations are a group of disorders frequently associated with aberrant glycosylation of alpha-dystroglycan. They include disease entities such a Walker-Warburg syndrome, muscle-eye-brain disease and various other clinical phenotypes. Different genes involved in glycosylation of alpha-dystroglycan are associated with these dystroglycanopathies. We describe a 5-year-old girl with psychomotor retardation, ataxia, spasticity, muscle weakness and increased serum creatine kinase levels. Immunhistochemistry of skeletal muscle revealed reduced glycosylated alpha-dystroglycan. Magnetic resonance imaging of the brain at 3.5 years of age showed increased T2 signal from supratentorial and infratentorial white matter, a hypoplastic pons and subcortical cerebellar cysts. By whole exome sequencing, the patient was identified to be compound heterozygous for a one-base duplication and a missense mutation in the gene B3GALNT2 (beta-1,3-N-acetylgalactosaminyltransferase 2; B3GalNAc-T2). This patient showed a milder phenotype than previously described patients with mutations in the B3GALNT2 gene. published online 2 October 2013