Glyc-O-genetics of Walker–Warburg syndrome.

van Reeuwijk J, Brunner HG, van Bokhoven H. Glyc-O-genetics of Walker–Warburg syndrome.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,fukutinandFKRP, 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 glycoproteinα-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. [ABSTRACT FROM AUTHOR]