Expanding the phenotype of GMPPB mutations

Macarena Cabrera-Serrano; Roula Ghaoui; Gianina Ravenscroft; Russell D Johnsen; Mark R Davis; Alastair Corbett; Stephen Reddel; Carolyn M Sue; Christina Liang; Leigh B Waddell; Simranpreet Kaur; Monkol Lek; Kathryn N North; Daniel G MacArthur; Phillipa J Lamont; Nigel F Clarke; Nigel G Laing

doi:10.1093/brain/awv013

Expanding the phenotype of GMPPB mutations

Brain. 2015 Apr;138(Pt 4):836-44. doi: 10.1093/brain/awv013. Epub 2015 Feb 12.

Authors

Macarena Cabrera-Serrano¹, Roula Ghaoui², Gianina Ravenscroft³, Russell D Johnsen⁴, Mark R Davis⁵, Alastair Corbett⁶, Stephen Reddel⁶, Carolyn M Sue⁷, Christina Liang⁷, Leigh B Waddell⁸, Simranpreet Kaur⁹, Monkol Lek¹⁰, Kathryn N North¹¹, Daniel G MacArthur¹², Phillipa J Lamont¹³, Nigel F Clarke⁸, Nigel G Laing³

Affiliations

¹ 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 [email protected].
² 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.
³ 1 Centre for Medical Research, University of Western Australia, Harry Perkins Institute of Medical Research, Perth, WA, Australia.
⁴ 6 Centre for Comparative Genomics, Murdoch University, Perth, Australia.
⁵ 7 Department of Diagnostic Genomics, Pathwest Laboratory Medicine WA. Perth, WA, Australia.
⁶ 8 Department of Neurology, Concord Repatriation Hospital, and Sydney Medical School, Sydney, Australia.
⁷ 5 Department of Neurology, Royal North Shore Hospital, Sydney, Australia.
⁸ 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 3 Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, Sydney, NSW 2145, Australia.
¹⁰ 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.
¹¹ 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.
¹² 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.
¹³ 13 Neurogenetic Unit, Department of Neurology, Royal Perth Hospital, Perth, WA, Australia.

PMID: 25681410
DOI: 10.1093/brain/awv013

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.

Keywords: GMPPB; alpha-dystroglycan; dystroglycanopathies; limb-girdle muscular dystrophy; rhabdomyolysis.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Child
Child, Preschool
Dystroglycans / genetics
Fatal Outcome
Female
Humans
Male
Middle Aged
Muscular Dystrophies, Limb-Girdle / diagnosis*
Muscular Dystrophies, Limb-Girdle / genetics*
Mutation / genetics*
Nucleotidyltransferases / genetics*
Pedigree
Phenotype*
Young Adult

Substances

Dystroglycans
Nucleotidyltransferases
mannose 1-phosphate guanylyltransferase