title: Glyc-O-genetics of Walker-Warburg syndrome.
abstract: Walker-Warburg syndrome (WWS) is the most severe of a group of multiple congenital anomaly disorders known as the cobblestone lissencephalies. These are characterized by congenital muscular dystrophy in conjunction with severe brain malformation and ocular abnormalities. In the last 3 years, important progress has been made towards the elucidation of the genetic causes of these disorders. Mutations in three genes, POMT1, fukutin and FKRP, have been described for WWS, which together account for approximately 20% of patients with Walker-Warburg. It has become evident that some of the underlying genes may cause a broad spectrum of phenotypes, ranging from limb girdle muscular dystrophy type 2I to WWS. In some cases, a genotype-phenotype correlation can be recognized. In line with the known or proposed functions of the resolved genes, all patients with cobblestone lissencephaly show defects in the O-linked glycosylation of the glycoprotein alpha-dystroglycan. Perhaps, the missing genes underlying the remainder of the unexplained WWS patients have also to be sought in the pathways involved in O-linked protein glycosylation.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical center, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van Reeuwijk
authors.forename: H G
authors.initials: HG
authors.lastname: Brunner
authors.forename: H
authors.initials: H
authors.lastname: van Bokhoven
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D001921:Brain / Q000002:abnormalities*; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism*; D018703:Founder Effect; D005838:Genotype; D006031:Glycosylation; D006801:Humans; D008364:Mannosyltransferases / Q000235:genetics*; D008565:Membrane Proteins; D009136:Muscular Dystrophies / Q000151:congenital; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics; D010430:Pentosyltransferases; D010641:Phenotype; D011506:Proteins / Q000235:genetics
chemical_list: C113587:FKTN protein, human; D008565:Membrane Proteins; D011506:Proteins; D049030:Dystroglycans; D008364:Mannosyltransferases; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase; C082696:protein O-mannosyltransferase; C443107:FKRP protein, human; D010430:Pentosyltransferases