Fanconi anaemia (FA) is a chronic and rare genetic condition caused by mutations in the FA DNA repair pathway. FA predisposes individuals to multiple serious health issues such as progressive bone marrow failure, early onset cancer, endocrine issues and physical abnormalities, however the clinical presentation is highly heterogeneous making diagnosis difficult. FA is caused by the loss of any one of 23 genes (‘FANC’ genes). The most common is FANCA, followed by FANCC and FANCG. The diagnosis of FA requires a positive chromosome breakage test which assesses genome instability due to the loss of function of the FA DNA repair pathway. More frequently, a positive diagnosis is followed by sequencing to find the causative mutation.
Most FA epidemiology studies have been performed in Europe and North America.
Here, we detail a cohort of 12 FA patients from Australian and New Zealand and compile it with published cases to give to give the first overview of FA in the region. In our study, FANCA was the most common subtype, this is representative of what has been recorded globally. Two patients in the study also report Aboriginal ancestry which has not been observed before. We have one previously unreported pathogenic mutation, which was found in FANCD2. We have multiple patients who have been diagnosed with FA, but the causative mutation is unknown. Haematological manifestations were common in our cohort of patients, many of which then needed a bone marrow transplant. Malignancies of the head and neck, gastrointestinal tract, liver and blood were also observed.
This initial report on Fanconi Anaemia in Australia and New Zealand highlights the common causative genes and heterogeneous clinical manifestations of the disorder. This will facilitate knowing which pathogenic variants are more likely to be segregating in Australasian populations as genetic screening approaches become more common.