Mutations and sequence variability of FAA gene in Japanese Fanconi anemia

• Published in: JOURNAL OF RADIATION RESEARCH 1998, Vol.39 (4), p.409-409
• Main Authors: Toshiko YAMADA, Akira TACHIBANA, Takesi KATO, Yosuke EJIMA, Masao S. SASAKI
• Format: Article
• Language: Japanese
• ISSN: 0449-3060

Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is genetically and clinically heterogeneous disease. At least 8 complementation groups (FA-A to FA-H) have been identified with their relative prevalence among the ethnical backgrounds. Recently, responsible genes, FAA and FAG, have been cloned. We studied mutations of the FAA gene by direct sequencing of cDNA with confirmation on genomic DNA in 15 unclassified Japanese FA patients. A total of 19 sequence alterations were identified, of which 10 were likely to be nonpathogenic polymorphism. Remaining 9 alterations, of which 8 were novel mutations, were assumed to be pathogenic and consisted of 2 missense mutations and 7 mutations resulting in truncation of gene product, demonstrating a wide allelic heterogeniety. The pathogenic mutations were found in 12 patients (80 %); they were either homozygous or compound heterozygous in 10 patients, apparently heterozygous in 2 patients and none in 3 patients. We conclude that the sequence variability is intrinsic to the FAA gene and that the relative prevalence of FA-A subtype is unusually high in Japanese FA patients.