Phenotypic consequences in black South African Fanconi anaemia patients homozygous for a FANCG 637-643 deletion mutation

Abstract

Fanconi anaemia (FA) is a genotypically and phenotypically heterogeneous genetic condition , characterized microscopically by chromosomal breakage and instability and usually inherited in an autosomal recessive manner. Affected individuals often present with a diverse variety of physical congenital abnormalities and most progress to haematological disease including bone marrow aplasia and myelodysplasia in early childhood. In South Africa, Black individuals with FA share a common causative founder deletion mutation in the Fanconi G gene (FANCG del) in 82% cases. They are thus an ideal patient cohort for a genotype-phenotype correlation study. Thirty Black patients, homozygous for FANCG del, were ascertained from haematology/oncology clinics in Johannesburg and Bloemfontein. They were subjected to a comprehensive clinical examination to a document their physical features. A concurrent review of each participant's hospital file allowed data to be collected regarding disease presentation and haematological progression .

Significant growth abnormalities and a high frequency of skin of skin pigmentary anomalies were found in the research cohort. Although subtle, anomalies of the eye, ears, and hands were noted in a high frequency. The overall physical phenotype does not appear to be appreciably different from that described in other Fanconi anaemia cohorts; however, affected Black individuals may present with more severe haematological indices and have poorer outcome that FA individuals of heterogeneous genotype. Further, it would appear that haematological disease progression cannot be predicted by the presence of abnormalities.