Mutations of the FAC polypeptide found in patients with FA. The wild-type FAC protein (558 amino acids) is shown schematically at the top. The indicated FAC alleles are also shown. The IVS4+4 A < T mutant allele encodes a protein with an in-frame deletion of 37 amino acids.80,91 The 322delG has a frame shift mutation in exon 1.77 This allele encodes an amino terminal truncated FAC protein with translation reinitiation from methionine 55.81 The IVS4+4 A < T mutation and 322delG account for approximately 75% of FAC mutations. Less common mutant alleles of FAC are also shown. At least three of these mutations fall in exon 14, encoding the carboxy terminus of the FAC protein. An allele with a C to T nucleotide substitution at base 808 (exon 6) is predicted to encode a protein with premature termination at amino acid 185.83 The 1806insA mutation is predicted to encode a truncated protein of 526 amino acids.86 A nucleotide substitution of T to C, at base 1913, encodes a protein with an (L554P) mutation.77 Recent studies suggest that this mutant protein is expressed in FAC cell lines91 and has dominant negative activity when overexpressed.94 This allele is the only known missense mutant and suggests that the carboxy terminus of FAC has functional relevance (see text). The relative frequency of these various FAC alleles has recently been described.82