title: Expanding the phenotype of GMPPB mutations.
abstract: Dystroglycanopathies are a heterogeneous group of diseases with a broad phenotypic spectrum ranging from severe disorders with congenital muscle weakness, eye and brain structural abnormalities and intellectual delay to adult-onset limb-girdle muscular dystrophies without mental retardation. Most frequently the disease onset is congenital or during childhood. The exception is FKRP mutations, in which adult onset is a common presentation. Here we report eight patients from five non-consanguineous families where next generation sequencing identified mutations in the GMPPB gene. Six patients presented as an adult or adolescent-onset limb-girdle muscular dystrophy, one presented with isolated episodes of rhabdomyolysis, and one as a congenital muscular dystrophy. This report expands the phenotypic spectrum of GMPPB mutations to include limb-girdle muscular dystrophies with adult onset with or without intellectual disability, or isolated rhabdomyolysis.
authors: 1 Centre for Medical Research, University of Western Australia, Harry Perkins Institute of Medical Research, Perth, WA, Australia 2 Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain Macarena.cabrera@uwa.edu.au.
authors: Macarena
authors: M
authors: Cabrera-Serrano
authors: 3 Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, Sydney, NSW 2145, Australia 4 Discipline of Paediatrics and Child Health, University of Sydney, Sydney, NSW 2006, Australia 5 Department of Neurology, Royal North Shore Hospital, Sydney, Australia.
authors: Roula
authors: R
authors: Ghaoui
authors: 1 Centre for Medical Research, University of Western Australia, Harry Perkins Institute of Medical Research, Perth, WA, Australia.
authors: Gianina
authors: G
authors: Ravenscroft
authors: 6 Centre for Comparative Genomics, Murdoch University, Perth, Australia.
authors: Russell D
authors: RD
authors: Johnsen
authors: 7 Department of Diagnostic Genomics, Pathwest Laboratory Medicine WA. Perth, WA, Australia.
authors: Mark R
authors: MR
authors: Davis
authors: 8 Department of Neurology, Concord Repatriation Hospital, and Sydney Medical School, Sydney, Australia.
authors: Alastair
authors: A
authors: Corbett
authors: 8 Department of Neurology, Concord Repatriation Hospital, and Sydney Medical School, Sydney, Australia.
authors: Stephen
authors: S
authors: Reddel
authors: 5 Department of Neurology, Royal North Shore Hospital, Sydney, Australia.
authors: Carolyn M
authors: CM
authors: Sue
authors: 5 Department of Neurology, Royal North Shore Hospital, Sydney, Australia.
authors: Christina
authors: C
authors: Liang
authors: 3 Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, Sydney, NSW 2145, Australia 4 Discipline of Paediatrics and Child Health, University of Sydney, Sydney, NSW 2006, Australia.
authors: Leigh B
authors: LB
authors: Waddell
authors: 3 Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, Sydney, NSW 2145, Australia.
authors: Simranpreet
authors: S
authors: Kaur
authors: 3 Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, Sydney, NSW 2145, Australia 4 Discipline of Paediatrics and Child Health, University of Sydney, Sydney, NSW 2006, Australia 9 Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA 10 Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors: Monkol
authors: M
authors: Lek
authors: 3 Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, Sydney, NSW 2145, Australia 11 Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia 12 Department of Paediatrics, University of Melbourne, Victoria, Australia.
authors: Kathryn N
authors: KN
authors: North
authors: 9 Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA 10 Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors: Daniel G
authors: DG
authors: MacArthur
authors: 13 Neurogenetic Unit, Department of Neurology, Royal Perth Hospital, Perth, WA, Australia.
authors: Phillipa J
authors: PJ
authors: Lamont
authors: 3 Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, Sydney, NSW 2145, Australia 4 Discipline of Paediatrics and Child Health, University of Sydney, Sydney, NSW 2006, Australia.
authors: Nigel F
authors: NF
authors: Clarke
authors: 1 Centre for Medical Research, University of Western Australia, Harry Perkins Institute of Medical Research, Perth, WA, Australia.
authors: Nigel G
authors: NG
authors: Laing
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D049030:Dystroglycans / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049288:Muscular Dystrophies, Limb-Girdle / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009713:Nucleotidyltransferases / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D055815:Young Adult
chemical_list: D049030:Dystroglycans; D009713:Nucleotidyltransferases; C026917:mannose 1-phosphate guanylyltransferase
keywords: GMPPB; alpha-dystroglycan; dystroglycanopathies; limb-girdle muscular dystrophy; rhabdomyolysis