GMPPB-Associated Dystroglycanopathy: Emerging Common Variants with Phenotype Correlation

Braden S Jensen; Tobias Willer; Dimah N Saade; Mary O Cox; Tahseen Mozaffar; Mena Scavina; Vikki A Stefans; Thomas L Winder; Kevin P Campbell; Steven A Moore; Katherine D Mathews

doi:10.1002/humu.22898

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GMPPB-Associated Dystroglycanopathy: Emerging Common Variants with Phenotype Correlation

Journal article

Open access

Peer reviewed

GMPPB-Associated Dystroglycanopathy: Emerging Common Variants with Phenotype Correlation

Braden S Jensen, Tobias Willer, Dimah N Saade, Mary O Cox, Tahseen Mozaffar, Mena Scavina, Vikki A Stefans, Thomas L Winder, Kevin P Campbell, Steven A Moore, …

Human mutation, Vol.36(12), pp.1159-1163

12/2015

DOI: 10.1002/humu.22898

PMCID: PMC4843780

PMID: 26310427

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Abstract

Mutations in GDP-mannose pyrophosphorylase B (GMPPB), a catalyst for the formation of the sugar donor GDP-mannose, were recently identified as a cause of muscular dystrophy resulting from abnormal glycosylation of α-dystroglycan. In this series, we report nine unrelated individuals with GMPPB-associated dystroglycanopathy. The most mildly affected subject has normal strength at 25 years, whereas three severely affected children presented in infancy with intellectual disability and epilepsy. Muscle biopsies of all subjects are dystrophic with abnormal immunostaining for glycosylated α-dystroglycan. This cohort, together with previously published cases, allows preliminary genotype-phenotype correlations to be made for the emerging GMPPB common variants c.79G>C (p.D27H) and c.860G>A (p.R287Q). We observe that c.79G>C (p.D27H) is associated with a mild limb-girdle muscular dystrophy phenotype, whereas c.860G>A (p.R287Q) is associated with a relatively severe congenital muscular dystrophy typically involving brain development. Sixty-six percent of GMPPB families to date have one of these common variants.

Muscular Dystrophies - metabolism

Genetic Association Studies

Humans

Child, Preschool

Dystroglycans - metabolism

Infant

Male

Muscle, Skeletal - metabolism

Muscular Dystrophies - genetics

Young Adult

Magnetic Resonance Imaging

Phenotype

Biopsy

Adolescent

Alleles

Brain - pathology

Nucleotidyltransferases - genetics

Female

Heterozygote

Muscular Dystrophies - diagnosis

Muscle, Skeletal - pathology

Mutation

Child

Details

Title: Subtitle: GMPPB-Associated Dystroglycanopathy: Emerging Common Variants with Phenotype Correlation
Creators: Braden S Jensen - Departments of Pediatrics and Neurology, University of Iowa Carver College of Medicine, Iowa City, Iowa
Tobias Willer - Howard Hughes Medical Institute, Departments of Molecular Physiology and Biophysics, Neurology, and Internal Medicine, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, Iowa
Dimah N Saade - Departments of Pediatrics and Neurology, University of Iowa Carver College of Medicine, Iowa City, Iowa
Mary O Cox - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa
Tahseen Mozaffar - Departments of Neurology and Orthopaedic Surgery, University of California, Irvine, California
Mena Scavina - Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware
Vikki A Stefans - Departments of Pediatrics and Physical Medicine and Rehabilitation, University of Arkansas for Medical Sciences College of Medicine, Little Rock, Arkansas
Thomas L Winder - Prevention Genetics, Marshfield, Wisconsin
Kevin P Campbell - Howard Hughes Medical Institute, Departments of Molecular Physiology and Biophysics, Neurology, and Internal Medicine, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, Iowa
Steven A Moore - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa
Katherine D Mathews - Departments of Pediatrics and Neurology, University of Iowa Carver College of Medicine, Iowa City, Iowa
Resource Type: Journal article
Publication Details: Human mutation, Vol.36(12), pp.1159-1163
DOI: 10.1002/humu.22898
PMID: 26310427
PMCID: PMC4843780
NLM abbreviation: Hum Mutat
ISSN: 1059-7794
eISSN: 1098-1004
Publisher: United States
Grant note: RC2 HL103010 / NHLBI NIH HHS RC2 HL102924 / NHLBI NIH HHS Howard Hughes Medical Institute UC2 HL102926 / NHLBI NIH HHS RC2 HL102923 / NHLBI NIH HHS RC2 HL102926 / NHLBI NIH HHS UC2 HL103010 / NHLBI NIH HHS UC2 HL102925 / NHLBI NIH HHS UC2 HL102924 / NHLBI NIH HHS U54 NS053672 / NINDS NIH HHS U54-NS053672 / NINDS NIH HHS U54 TR001013 / NCATS NIH HHS UC2 HL102923 / NHLBI NIH HHS RC2 HL102925 / NHLBI NIH HHS U54-TR001013 / NCATS NIH HHS
Language: English
Date published: 12/2015
Academic Unit: Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Neurology (Pediatrics)
Record Identifier: 9984020607602771

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