Fanconi anemia A due to a novel frameshift mutation in hotspot motifs: lack of FANCA protein

Homozygosity for a frameshift mutation at codon 1213 of FANCA gene was identified in a Turkish patient. Immunoprecipitation-western blot analysis showed the complete absence of the FANCA protein band. This novel mutation, a deletion of T at position 3639 in exon 37 (3639delT), is responsible for the disease and causes premature termination of translation 32 aa downstream. The deletion is (i) the T residue of 2 overlapping TGAGGC and CCTG hot spot motifs, (ii) flanked by several direct repeats, (iii) surrounded by the highly GC rich region that have frequently been identified at the site of human DNA deletions. The patient is the third living child of a first degree cousin marriage. The major abnormalities of the patient at the age of 6 months were growth retardation, microcephaly, hypoplastic right thumb, distal displacements of both thumbs and pelvic displacement of left kidney. Hematological presentation of the disease started before the age of 4 years.