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

• Published in: Neuromuscular disorders : NMD 2005-04, Vol.15 (4), p.271-275
• Main Authors: Balci, Burcu, Uyanik, Gökhan, Dincer, Pervin, Gross, Claudia, Willer, Tobias, Talim, Beril, Haliloglu, Göknur, Kale, Gülsev, Hehr, Ute, Winkler, Jürgen, Topaloğlu, Haluk
• Format: Article
• Language: English
• Subjects: A200P mutation; Adolescent; Adult; Alanine - genetics; Alleles; Child; DNA Mutational Analysis - methods; Female; Humans; Hypoglycosylation of α-dystroglycan; Intellectual Disability - genetics; Intellectual Disability - physiopathology; LGMD2; Male; Mannosyltransferases - genetics; Models, Molecular; Muscular Dystrophies, Limb-Girdle - genetics; Muscular Dystrophies, Limb-Girdle - physiopathology; Mutation - genetics; Phenotype; Polymorphism, Single Nucleotide; POMT1 gene; Proline - genetics; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - biosynthesis; WWS
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/j.nmd.2005.01.013

Mutations of the protein O-mannosyltransferase ( POMT1) gene affect glycosylation of α-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 α-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.