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Screening of mutations of hemophilia A in 40 Italian patients: a novel G-to-A mutation in intron 10 of the F8 gene as a putative cause of mild hemophilia a in southern Italy

2008; Lippincott Williams & Wilkins; Volume: 19; Issue: 3 Linguagem: Inglês

10.1097/mbc.0b013e3282f234ab

1473-5733

Rosa Santacroce, Rita Santoro, Francesco Sessa, Piergiorgio Iannaccaro, Michelina Sarno, Vittoria Longo, Anna Gallone, Gennaro Vecchione, G. Muleo, Maurizio Margaglione,

Platelet Disorders and Treatments

Hemophilia A is an X-linked bleeding disorder caused by widespread mutations in the human coagulation factor 8 gene. We have searched for mutations in factor 8 gene DNAs from 40 unrelated Italian patients with hemophilia A. All patients came from the same region (Calabria) and were followed-up at the same hemophilia center. Of the 40 patients, 20 (50%) had severe hemophilia A, 19 (47.5%) had moderate hemophilia A, and one (2.5%) had mild hemophilia A. All patients were first screened for the common intron 22 and intron 1 inversions. Inversion-negative samples were screened for point mutations by direct sequencing of all coding regions and intron-exon boundaries of the factor 8 gene. Mutations previously reported as causative of hemophilia A were identified in 14 of the 40 patients. These included five (12.5%) intron 22 inversions, one (2.5%) small deletion, one (2.5%) small insertion and seven (17.5%) point mutations. In all patients with moderate and mild hemophilia A, a nucleotide change in the c.1538 -18G>A in intron 10, not reported in the HAMSTeRS factor 8 mutation database (http://europium.csc.mrc.ac.uk/), was found. The G-to-A change predicts the appearance of a new acceptor splice site. We have also demonstrated that all patients share a common haplotype, suggesting that the mutation probably occurred in a single ancestor. In conclusion, we suggest that the c.1538-18G>A transition can be the putative mutation, which probably occurred in a common ancestor and then spread in neighbours, in patients with moderate-mild hemophilia A investigated in the present study.