IDENTIFICATION OF NOVEL MISSENSE MUTATIONS IN NORRIE-DISEASE GENE ASSOCIATED WITH ONE X-LINKED AND 4 SPORADIC CASES OF FAMILIAL EXUDATIVE VITREORETINOPATHY

X-linked Familial Exudative Vitreoretinopathy (XLFEVR) is a hereditary eye disorder that affects both the retina and the vitreous body. It i s characterized by an abnormal vascularization of the peripheral retin a, It has been previously shown by linkage and candidate gene analysis that XLFEVR and Norrie disease are allelic. In this report we describ e four novel mutations (R41K, H42R, K58N, and Y120C) in the Norrie dis ease gene associated with one X-linked and four sporadic cases of FEVR . One mutation (H42R) was found to be segregating with the disease in three generations (X-linked family), and the others are sporadic. Thes e sequence alterations changed the encoded amino acids in the Norrie d isease protein and were not found in 17 unaffected family members or i n 36 randomly selected normal individuals. This study provides additio nal evidence that mutations in the same gene fan result in FEVR and No rrie disease. It also demonstrates that it may be beneficial for clini cal diagnosis to screen for mutations in the Norrie disease gene in sp oradic FEVR cases. (C) 1997 Wiley-Liss, Inc.