title: The IVS4 + 4 A to T mutation of the fanconi anemia gene FANCC is not associated with a severe phenotype in Japanese patients.
abstract: Fanconi anemia (FA) is an autosomal recessive disease characterized by congenital anomalies, aplastic anemia, and a susceptibility to leukemia. There are at least 8 complementation groups (A through H). Extensive analyses of the FA group C gene FANCC in Western countries revealed that 10% to 15% of FA patients have mutations of this gene. The most common mutation is IVS4 + 4 A to T (IVS4), a splice mutation in intron 4, which has been found only in patients of Ashkenazi Jewish ancestry. When we screened 29 Japanese patients (20 unrelated patients and 4 families) using polymerase chain reaction-single strand conformation polymorphism, we found 8 unrelated patients homozygous for IVS4. This is apparently the first non-Ashkenazi-Jewish population for whom this mutation has been detected. The Ashkenazi Jewish patients homozygous for IVS4 have a severe phenotype, in comparison with other FA patients. Our analyses of Japanese patients indicate no significant difference between IVS4 homozygotes and other patients with regard to severity of a clinical phenotype. Thus, ethnic background may have a significant effect on a clinical phenotype in FA patients carrying the same mutation. (Blood. 2000;95:1493-1498)
authors.affiliation: Departments of Pediatrics and Hematology/Oncology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Futaki
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: H
authors.initials: H
authors.lastname: Yagasaki
authors.forename: T
authors.initials: T
authors.lastname: Toda
authors.forename: M
authors.initials: M
authors.lastname: Yabe
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: S
authors.initials: S
authors.lastname: Asano
authors.forename: T
authors.initials: T
authors.lastname: Nakahata
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D017398:Alternative Splicing; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002648:Child; D000013:Congenital Abnormalities / Q000235:genetics*; D004268:DNA-Binding Proteins; D005060:Europe / Q000208:ethnology; D005091:Exons; D005190:Family; D005199:Fanconi Anemia / Q000235:genetics*; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D005260:Female; D006720:Homozygote; D006801:Humans; D007438:Introns; D007564:Japan; D007585:Jews / Q000235:genetics; D008297:Male; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C497651:FANCC protein, human; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; D011506:Proteins