Clinical Features and Molecular Characterization of a Patient With Muscle-Eye-Brain Disease

Abstract

Muscle-eye-brain (MEB) disease is a congenital muscular dystrophy characterized by structural brain and eye defects. Here, we describe a 12-year-old boy with partial agenesis of corpus callosum, ventriculomegaly, flattened brainstem, diffuse pachygyria, blindness, profound cognitive deficiencies and generalized muscle weakness, yet without a clear dystrophic pattern on muscle biopsy. There was no glycosylation of α-dystroglycan and the genetic screening revealed a novel truncating mutation, c.1545delC (p.Tyr516Thrfs*21), and a previously identified missense mutation, c.1469G>A (p.Cys490Tyr), in the protein O-mannose beta-1,2-Nacetylglucosaminyltransferase 1 (POMGNT1) gene. These findings broaden the clinical spectrum of MEB to include pronounced hypotonia with severe brain and eye malformations, yet with mild histopathological changes in the muscle specimen, despite the absence of glycosylated α-dystroglycan.

Matriglycan: a novel polysaccharide that links dystroglycan to the basement membrane

“…Although dystroglycan-deficient mice recapitulate phenotypes that are present in the brain and muscle of dystroglycanopathy patients ( Kanagawa et al 2004 ; Satz et al 2008 ; Nguyen et al 2013 ), these findings suggest that the clinical manifestations observed among patients with mutations in POMT1, POMT2 and POMGNT1 may differ slightly from those observed in dystroglycanopathy patients with mutations that affect other glycosyltransferases. This notion is supported by the discovery of a patient who had a POMGNT1 mutation and exhibited profound cognitive deficiencies as well as structural defects in the brain and eyes, but had only mild myopathic changes without clear signs of dystrophy ( Raducu et al 2014 ).…”