van Reeuwijk J, Brunner H G, van Bokhoven H
Department of Human Genetics, Radboud University Nijmegen Medical center, The Netherlands.
Clin Genet. 2005 Apr;67(4):281-9. doi: 10.1111/j.1399-0004.2004.00368.x.
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.
沃克-沃尔堡综合征（WWS）是一组被称为鹅卵石样无脑回畸形的多发性先天性异常疾病中最严重的一种。这些疾病的特征是先天性肌营养不良，同时伴有严重的脑畸形和眼部异常。在过去三年里，在阐明这些疾病的遗传病因方面取得了重要进展。已发现WWS患者中三个基因POMT1、福金蛋白和FKRP发生突变，这些突变共同约占沃克-沃尔堡综合征患者的20%。很明显，一些潜在基因可能导致广泛的表型，从2I型肢带型肌营养不良到WWS。在某些情况下，可以识别出基因型-表型相关性。根据已解析基因的已知或推测功能，所有鹅卵石样无脑回畸形患者的糖蛋白α-肌营养不良蛋白的O-连接糖基化均存在缺陷。也许，其余无法解释的WWS患者的缺失基因也应在O-连接蛋白糖基化相关途径中寻找。
