Mild POMGnT1 mutations underlie a novel limb-girdle muscular dystrophy variant.
BACKGROUND
Mutations in protein-O-mannose-beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) have been found in muscle-eye-brain disease, a congenital muscular dystrophy with structural eye and brain defects and severe mental retardation.


OBJECTIVE
To investigate whether mutations in POMGnT1 could be responsible for milder allelic variants of muscular dystrophy.


METHODS
Screening for mutations in POMGnT1.


METHODS
Tertiary neuromuscular unit.


METHODS
A patient with limb-girdle muscular dystrophy phenotype, with onset at 12 years of age, severe myopia, normal intellect, and decreased alpha-dystroglycan immunolabeling in skeletal muscle.


RESULTS
A homozygous POMGnT1 missense mutation (c.1666G>A, p.Asp556Asn) was identified. Enzyme studies of the patient's fibroblasts showed an altered kinetic profile, less marked than in patients with muscle-eye-brain disease and in keeping with the relatively mild phenotype in our patient.


CONCLUSIONS
Our findings widen the spectrum of disorders known to result from mutations in POMGnT1 to include limb-girdle muscular dystrophy with no mental retardation. We propose that this condition be known as LGMD2M. The enzyme assay used to diagnose muscle-eye-brain disease may not detect subtle abnormalities of POMGnT1 function, and additional kinetic studies must be carried out in such cases.
Clement
Emma M
EM
Dubowitz Neuromuscular Unit, Department of Paediatrics, Hammersmith Hospital, Imperial College London, Du Cane Road, London W12 ONN, England.
Godfrey
Caroline
C
Tan
Jenny
J
Brockington
Martin
M
Torelli
Silvia
S
Feng
Lucy
L
Brown
Susan C
SC
Jimenez-Mallebrera
Cecilia
C
Sewry
Caroline A
CA
Longman
Cheryl
C
Mein
Rachael
R
Abbs
Steve
S
Vajsar
Jiri
J
Schachter
Harry
H
Muntoni
Francesco
F
D000483:Alleles; D015153:Blotting, Western; D002648:Child; D004252:DNA Mutational Analysis; D049030:Dystroglycans / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology; D005820:Genetic Testing; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000150:complications / Q000235:genetics* / Q000523:psychology; D009154:Mutation; D020125:Mutation, Missense / Q000235:genetics; D009216:Myopia / Q000209:etiology; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D010641:Phenotype
D049030:Dystroglycans; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase