Novel mutations of the FANCG gene causing alternative splicing in Japanese Fanconi anemia.

摘要: Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is genetically clinically heterogeneous disease. At least eight complementation groups (FA-A FA-H) have been identified. Previously, we studied mutations of the FANCA gene, responsible for FA-A, found pathogenic in 12 15 unclassified Japanese FA patients. Here, further additional 5 patients sequence alterations gene 2 them. We analyzed FANCC FANCG genes, FA-C FA-G, respectively, remaining 6 Although there was no these patients, two novel causing aberrant RNA splicing, were detected One base substitution from G C invariant GT dinucleotides at splice donor site intron 3, resulting skipping exon as well exons 3 4. The other T 8, creating nonsense codon (Q356X). This mutation resulted exclusion 18 nucleotides containing mRNA, without affecting splicing potential either authentic or cryptic site. Collectively, 14 20 belong FA-A group, FA-G none belongs group.