POSITIVE DIEPOXYBUTANE TEST IN ONLY ONE OF 2 BROTHERS FOUND TO BE COMPOUND HETEROZYGOTES FOR FANCONI ANEMIA COMPLEMENTATION GROUP-C MUTATIONS

Fanconi's anaemia (FA) is an autosomal recessive disorder characterize d by diverse congenital abnormalities, the development of progressive bone marrow failure, and an increased predisposition to malignancy, pa rticularly acute leukaemia. The FA phenotype is so variable that diagn osis on the basis of clinical manifestations alone can be difficult. T he modern diagnosis of FA no longer rests entirely on the constellatio n of clinical and haematological abnormalities first described by Fanc oni, but depends on finding elevated chromosomal breakage after incuba tion of peripheral blood lymphocytes with the chemical clastogens diep oxybutane (DEB) or mitomycin-C (MMC). The cloning of the gene for FA c omplementation group C [FAC] provides an opportunity to test the valid ity of the 'DEB test' which in recent times has become the main arbite r as to whether a patient is classified as FA or non-FA. We report on two brothers with similar clinical and haematological features who hav e both been identified as compound heterozygotes for the FAC mutations L554P and Delta G322, but only one of the brothers has a positive DEB test. On the basis of the DEB test one would be classified as FA and the other as non-FA. The time has come to re-evaluate the diagnostic c riteria of 'Fanconi's anaemia'.