A novel missense mutation in POMT1 modulates the severe congenital muscular dystrophy phenotype associated with POMT1 nonsense mutations.
Mutations in POMT1 lead to a group of neuromuscular conditions ranging in severity from Walker-Warburg syndrome to limb girdle muscular dystrophy. We report two male siblings, ages 19 and 14, and an unrelated 6-year old female with early onset muscular dystrophy and intellectual disability with minimal structural brain anomalies and no ocular abnormalities. Compound heterozygous mutations in POMT1 were identified including a previously reported nonsense mutation (c.2167dupG; p.Asp723Glyfs*8) associated with Walker-Warburg syndrome and a novel missense mutation in a highly conserved region of the protein O-mannosyltransferase 1 protein (c.1958C>T; p.Pro653Leu). This novel variant reduces the phenotypic severity compared to patients with homozygous c.2167dupG mutations or compound heterozygous patients with a c.2167dupG mutation and a wide range of other mutant POMT1 alleles.
Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, United States; Seattle Children's Hospital, Seattle, WA, United States.
Stephanie E
SE
Wallace
Department of Laboratories, Seattle Children's Hospital, Seattle, WA, United States.
Jessie H
JH
Conta
Prevention Genetics, Marshfield, WI, United States.
Thomas L
TL
Winder
Howard Hughes Medical Institute and Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States.
Tobias
T
Willer
Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States.
Jamie M
JM
Eskuri
Department of Neurosciences University of California, San Diego, La Jolla, CA, United States; Department of Pediatrics, University of California, San Diego, La Jolla, CA, United States; Rady Children's Hospital San Diego, CA, United States.
Richard
R
Haas
Department of Pathology, Seattle Children's Hospital, Seattle, WA, United States.
Kathleen
K
Patterson
Howard Hughes Medical Institute and Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States; Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States; Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States.
Kevin P
KP
Campbell
Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States.
Steven A
SA
Moore
Department of Neurology, University of Washington, Seattle, WA, United States; Department of Pediatrics, University of Washington, Seattle, WA, United States; Seattle Children's Hospital, Seattle, WA, United States. Electronic address: sgospe@uw.edu.
Sidney M
SM
Gospe
D000293:Adolescent; D001921:Brain / Q000473:pathology; D002478:Cells, Cultured; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008364:Mannosyltransferases / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D020125:Mutation, Missense; D010641:Phenotype; D012720:Severity of Illness Index; D035781:Siblings; D055815:Young Adult
D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase
Congenital muscular dystrophy; Dystroglycanopathy; Limb girdle muscular dystrophy; POMT1; Protein O-mannosylation; Walker–Warburg syndrome