|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1996 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1995 : ¥1,200,000 (Direct Cost : ¥1,200,000)
We studied Norrie disease (ND) gene in seven families with typical clinical features of ND,three families with X-linked familial exudative vitreoretinopathy (FEVR) and a male patient with bilateral primary hyperplastic vitreous (PHPV). In patients examined, four families showed a variety of ND gene mutations. 1) Two independent ND families showed a mutation at the initiation codon of the ND gene (ATG to GTG). These two families had lived in the south-western area of the country for at least several centuries and they claimed no relationship. It is, however, possible in view of the rarity of the disease that the identical gene mutation represents a founder effect. 2) One ND family in Tokyo area showed a missense mutation at the codon 95 (TGC to CGC) of the ND gene. Relevant amino acid (cystein) has been suggested to be significant for the conformation of the ND protein. 3) In above three families, specified PCR-restriction detection revealed the mutated allele status ; hemizygote in patients (X'Y), heterozygote in carriers (X'X), and wild types (XY or XX). 4) One ND family in near Tokyo area had a presumed tandem duplication. Results from SSCP,cloned nucleotide sequencing, Southern blots, and long PCR suggested a large scale duplication overlapping exon 2 of the ND gene. We could not determine the size or the duplication junction. However, DXS1003, a DNA polymorphic marker near the ND gene showed a common repeat in two patients in this family, compatible with X-linked transmission near ND allele. 5) Remaining families of ND,FEVR,or PHPV showed only wild-type nucleotide sequences in the coding exons of the ND gene. 6) There is a wide variability of ND mutations among families, and phenotype-genotype correlation remains to be elucidated.