WISKOTT-ALDRICH SYNDROME IN A FAMILY WITH FANCONI-ANEMIA

Thrombocytopenia may be the presenting finding for both Wiskott-Aldric h syndrome and Fanconi anemia, We examined a sibship of four boys who had features of both of these hematologic disorders, Peripheral blood lymphocytes from three of the boys demonstrated DNA instability when c ultured with diepoxybutane, confirming the diagnosis of Fanconi anemia in these patients, However, results of linkage analysis and X chromos ome inactivation studies were consistent with the diagnosis of Wiskott -Aldrich syndrome in two of the boys, including one of the boys with F anconi anemia, These findings could be attributed to the occurrence of two rare genetic disorders in a single family or to an unusual varian t of Fanconi anemia, The recent identification of the Wiskott-Aldrich gene permitted us to address this question directly, Epstein-Barr viru s-transformed cell lines from the two boys thought to have Wiskott-Ald rich syndrome on the basis of linkage analysis failed to express trans cripts for the Wiskott-Aldrich gene, Genomic DNA from these two patien ts demonstrated a G insertion in the tenth exon of the Wiskott-Aldrich gene, resulting in a frameshift and a premature stop codon, Surprisin gly, the patient with Fanconi anemia and a null mutation in the Wiskot t-Aldrich gene had typical Fanconi anemia but mild Wiskott-Aldrich syn drome.