title: 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.
abstract: 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.
authors.affiliation: Department of Medical Biology, Hacettepe University, Faculty of Medicine, Sihhiye, 06100 Ankara, Turkey.
authors.forename: Burcu
authors.initials: B
authors.lastname: Balci
authors.forename: Gökhan
authors.initials: G
authors.lastname: Uyanik
authors.forename: Pervin
authors.initials: P
authors.lastname: Dincer
authors.forename: Claudia
authors.initials: C
authors.lastname: Gross
authors.forename: Tobias
authors.initials: T
authors.lastname: Willer
authors.forename: Beril
authors.initials: B
authors.lastname: Talim
authors.forename: Göknur
authors.initials: G
authors.lastname: Haliloglu
authors.forename: Gülsev
authors.initials: G
authors.lastname: Kale
authors.forename: Ute
authors.initials: U
authors.lastname: Hehr
authors.forename: Jürgen
authors.initials: J
authors.lastname: Winkler
authors.forename: Haluk
authors.initials: H
authors.lastname: Topaloğlu
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D011392:Proline; D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase; D000409:Alanine