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

2000; Elsevier BV; Volume: 95; Issue: 4 Linguagem: Inglês

10.1182/blood.v95.4.1493.004k35_1493_1498

1528-0020

Makoto Futaki, Takayuki Yamashita, Hiroshi Yagasaki, Tatsushi Toda, Miharu Yabe, Shunichi Kato, Shigetaka Asano, Tatsutoshi Nakahata,

Porphyrin Metabolism and Disorders

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.