title: Two common founder mutations of the fanconi anemia group G gene FANCG/XRCC9 in the Japanese population.
abstract: Fanconi anemia (FA) is a rare autosomal recessive disorder of hematopoiesis with eight complementation groups (FA-A, B, C, D1, D2, E, F and G). To date, seven of the FA genes have been identified. Although extensive analyses in Western countries revealed that the subgroup prevalence and mutational spectrum vary depending on the ethnic background, not much data is available on Asian populations. In the present study, 45 unrelated FA families in Japan were screened for FA gene mutations and 10 families with biallelic pathogenic mutations of FANCG/XRCC9, the gene for FA-G, were identified. A splice mutation IVS3+1G>C was detected in all 9 Japanese families, among whom 4 were homozygous and 5 were heterozygous. Among the heterozygotes, three carried 1066C>T in the second allele. In addition, a family homozygous for 1066C>T with Korean ethnicity was identified. Haplotype analysis by means of 9 microsatellite markers spanning the FANCG locus indicates that IVS3+1G>C and 1066C>T are in complete association with distinct ancestry haplotypes. Our data suggest that IVS3+1G>C arose in the Japanese ancestors at a relatively early time, whereas 1066C>T later on migrated from Korea. The two founder mutations with distinct origins account for most of FANCG mutant alleles in the Japanese population.
authors.affiliation: Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagasaki
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Oda
authors.forename: Daiki
authors.initials: D
authors.lastname: Adachi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakajima
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Asano
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005192:Family Health; D005199:Fanconi Anemia / Q000235:genetics* / Q000473:pathology; D052241:Fanconi Anemia Complementation Group G Protein; D005260:Female; D018703:Founder Effect; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation
chemical_list: D004268:DNA-Binding Proteins; C499909:FANCG protein, human; D052241:Fanconi Anemia Complementation Group G Protein; D004247:DNA