Variable pathogenicity of exon 43del (FAA) in four Fanconi anaemia patients within a consanguineous family

Four Fanconi anaemia group A (FAA) patients within two related consanguineo us families are presented: the propositus (male, 13 years, transplanted at age 10), and his three cousins (one male, 8 years, and two female newborns) . Assignment of the patients to FAA was based on the functional complementa tion analysis by somatic cell hybridization and confirmed by mutation scree ning showing a homozygous deletion of exon 43 (4267-4404del) in the FAA gen e to be present in all four patients. The newborn patients had been diagnos ed prenatally by DNA analysis. in spite of identical molecular pathology an d close familial relationship the clinical phenotypes of the four patients were not concordant. Discordant symptoms included birthweight, pigmentation abnormalities, skeletal, renal and genital abnormalities, whereas microcep haly and possibly the haematological course were concordant. Differences in environmental conditions and/or genetic make-up along with chance effects during development may explain discordant phenotypes despite identical mole cular pathology in these patients. However, our results do not rule out the possibility that the exon 43del mutation may have prognostic Value for the haematological course of the disease.