Clinical Features and Molecular Characterization of a Patient With Muscle-Eye-Brain Disease: A Novel Mutation in the POMGNT1 Gene. (February 2014)

• Record Type: Journal Article
• Authors: Raducu, Madalina; Cotarelo, Rocío P.; Simón, Rogelio; Camacho, Ana; Rubio-Fernández, Marcos; Hernández-Laín, Aurelio; Cruces, Jesús
• Is Part Of: Journal of child neurology. Volume 29:Number 2(2014:Feb.)
• Page Start: 289
• Page End: 294
• Publication Date: 2014-02
• Subjects: dystroglycan -- dystroglycanopathy -- muscle-eye-brain disease -- POMGNT1 -- glycosylation; Nervous system -- Diseases -- Periodicals; 618.928
• DOI: 10.1177/0883073813509119
• Languages: English
• ISSNs: 0883-0738

Abstract

Muscle-eye-brain 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 brain stem, 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- N -acetylglucosaminyltransferase 1 ( POMGNT1 ) gene. These findings broaden the clinical spectrum of muscle-eye-brain disease to include pronounced hypotonia with severe brain and eye malformations, yet with mild histopathologic changes in the muscle specimen, despite the absence of glycosylated α-dystroglycan.