The IVS4+4 A to T mutation of the Fanconi anemia gene FANCC is not associated with a severe phenotype in Japanese patients

Fanconi anemia (FA) is an autosomal recessive disease characterized by cong enital 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 4A to T (IVS4), a splice mutation in intron 4, which has been found only i n patients of Ashkenazi Jewish ancestry. When we screened 29 Japanese patie nts (20 unrelated patients and 4 families) using polymerase chain reaction- single strand conformation polymorphism, we found 8 unrelated patients homo zygous for IVS4. This is apparently the first non-Ashkenazi-Jewish populati on for whom this mutation has been detected. The Ashkenazi Jewish patients homozygous for IVS4 have a severe phenotype, in comparison with other FA pa tients. Our analyses of Japanese patients indicate no significant differenc e between IVS4 homozygotes and other patients with regard to severity of a clinical phenotype. Thus, ethnic background may have a significant effect o n a clinical phenotype in FA patients carrying the same mutation. (C) 2000 by The American Society of Hematology.