An autosomal recessive limb girdle muscular dystrophy (LGMD2) with mild mental retardation is allelic to Walker-Warburg syndrome (WWS) caused by a mutation in the POMT1 gene.
Mutations of the protein O-mannosyltransferase (POMT1) gene affect glycosylation of alpha-dystroglycan, leading to Walker-Warburg syndrome, a lethal disorder in early life with severe congenital muscular dystrophy, and brain and eye malformations. Recently, we described a novel form of recessive limb girdle muscular dystrophy with mild mental retardation, associated with an abnormal alpha-dystroglycan pattern in the muscle, suggesting a glycosylation defect. Here, we present evidence that this distinct phenotype results from a common mutation (A200P) in the POMT1 gene. Our findings further expand the phenotype of glycosylation disorders linked to POMT1 mutations. Furthermore, the A200P mutation is part of a conserved core haplotype, indicating an ancestral founder mutation.
Balci
Burcu
B
Department of Medical Biology, Hacettepe University, Faculty of Medicine, Sihhiye, 06100 Ankara, Turkey.
Uyanik
Gökhan
G
Dincer
Pervin
P
Gross
Claudia
C
Willer
Tobias
T
Talim
Beril
B
Haliloglu
Göknur
G
Kale
Gülsev
G
Hehr
Ute
U
Winkler
Jürgen
J
Topaloğlu
Haluk
H
D000293:Adolescent; D000328:Adult; D000409:Alanine / Q000235:genetics; D000483:Alleles; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008364:Mannosyltransferases / Q000235:genetics*; D008958:Models, Molecular; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011392:Proline / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D012333:RNA, Messenger; D011392:Proline; D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase; D000409:Alanine