title: TMEM5-associated dystroglycanopathy presenting with CMD and mild limb-girdle muscle involvement.
abstract: The dystroglycanopathies, which are caused by reduced glycosylation of alpha-dystroglycan, are a heterogeneous group of neurodegenerative disorders characterized by variable brain and skeletal muscle involvement. Recently, mutations in TMEM5 have been described in severe dystroglycanopathies. We present the clinical, molecular and neuroimaging features of an Italian boy who had delayed developmental milestones with mild limb-girdle muscle involvement, bilateral frontotemporal polymicrogyria, moderate intellectual disability, and no cerebellar involvement. He also presented a cochlear dysplasia and harbored a reported mutation (p.A47Rfs*42) in TMEM5, detected using targeted next-generation sequencing. The relatively milder muscular phenotype and associated structural brain abnormalities distinguish this case from previously reported patients with severe dystroglycanopathies and expand the spectrum of TMEM5-associated disorders.
authors.affiliation: IRCCS Stella Maris, Pisa, Italy.
authors.forename: Guja
authors.initials: G
authors.lastname: Astrea
authors.affiliation: IRCCS Stella Maris, Pisa, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Pezzini
authors.affiliation: Department of Experimental Medicine, Cardiomyology and Medical Genetics, Second University of Naples, Naples, Italy.
authors.forename: Ester
authors.initials: E
authors.lastname: Picillo
authors.affiliation: IRCCS Stella Maris, Pisa, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Pasquariello
authors.affiliation: IRCCS Stella Maris, Pisa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Moro
authors.affiliation: Department of Experimental Medicine, Cardiomyology and Medical Genetics, Second University of Naples, Naples, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Ergoli
authors.affiliation: Department of Experimental Medicine, Cardiomyology and Medical Genetics, Second University of Naples, Naples, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: D'Ambrosio
authors.affiliation: Unit for Neuromuscular and Neurodegenerative Disorders, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: D'Amico
authors.affiliation: Department of Experimental Medicine, Cardiomyology and Medical Genetics, Second University of Naples, Naples, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Politano
authors.affiliation: IRCCS Stella Maris, Pisa, Italy. Electronic address: filippo3364@gmail.com.
authors.forename: Filippo Maria
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D000293:Adolescent; D001921:Brain / Q000000981:diagnostic imaging; D049030:Dystroglycans / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009136:Muscular Dystrophies / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology*; D010430:Pentosyltransferases; D010641:Phenotype
chemical_list: D008565:Membrane Proteins; D049030:Dystroglycans; D010430:Pentosyltransferases; C578283:RXYLT1 protein, human
keywords: Cochlear dysplasia; Congenital muscular dystrophy; Limb-girdle muscle weakness; Polymicrogyria; TMEM5