title: Clinical features and molecular characterization of a patient with muscle-eye-brain disease: a novel mutation in the POMGNT1 gene.
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.
authors.affiliation: 1Departamento de Bioquímica, Instituto de Investigaciones Biomédicas "Alberto Sols" UAM-CSIC, IdIPAZ, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Madalina
authors.initials: M
authors.lastname: Raducu
authors.forename: Rocío P
authors.initials: RP
authors.lastname: Cotarelo
authors.forename: Rogelio
authors.initials: R
authors.lastname: Simón
authors.forename: Ana
authors.initials: A
authors.lastname: Camacho
authors.forename: Marcos
authors.initials: M
authors.lastname: Rubio-Fernández
authors.forename: Aurelio
authors.initials: A
authors.lastname: Hernández-Laín
authors.forename: Jesús
authors.initials: J
authors.lastname: Cruces
mesh_terms: D001706:Biopsy; D001921:Brain / Q000473:pathology; D002648:Child; D004252:DNA Mutational Analysis; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D052097:Quadriceps Muscle / Q000378:metabolism / Q000473:pathology; D058494:Walker-Warburg Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase
keywords: POMGNT1; dystroglycan; dystroglycanopathy; glycosylation; muscle-eye-brain disease