A NONSENSE MUTATION AND EXON SKIPPING IN THE FANCONI-ANEMIA GROUP-C GENE

Fanconi anaemia (FA) is an autosomal recessive disorder associated wit h bone-marrow failure and hypersensitivity to DNA cross-linking agents . At least four complementation groups have been defined, and a cDNA w hich corrects the defect in group C cells (FACC) has recently been iso lated. We have screened the FACC coding sequence for mutations in FA p atients and found one patient to be homozygous for a nonsense mutation in exon 6 of the FACC coding sequence (R185X). Exon 6 was spliced out of a proportion of this patient's transcripts, providing further supp ort for the proposal that nonsense mutations may alter splice site sel ection. Alternatively spliced transcripts which lacked exon 13 were de tected in both patients and controls.