SEQUENCE VARIATIONS IN THE FANCONI-ANEMIA GENE, FAC - PATHOGENICITY OF 1806INSA AND R548X AND RECOGNITION OF D195V AS A POLYMORPHIC VARIANT

Fanconi anaemia (FA) is a rare autosomal recessive disorder associated with diverse clinical symptoms, increased chromosomal instability and a marked hypersensitivity to crosslinking agents. At least five compl ementation groups have been defined, the gene for group C (FAC) being the only FA gene cloned thus far. Several sequence variations have bee n detected in FA patients, whose assignment to group C, however, had n ot been ascertained by complementation studies. Using a functional ass ay, in which we tested the capacity of a variant sequence to correct t he defect in FA-C lymphoblasts, we provide evidence for the pathogenic status of 1806insA and R548X and for non-pathogenicity of D195V.