DIAMOND-BLACKFAN ANEMIA - GENETIC HOMOGENEITY FOR A GENE ON CHROMOSOME 19Q13 RESTRICTED TO 1.8 MB

Diamond-Blackfan anaemia (DEA; MIM#205900) is a rare disorder manifest ed as a pure red-cell aplasia in the neonatal period or in infancy(1-3 ). The clinical hallmark of DBA is a selective decrease in erythroid p recursors and anaemia. Other lineages are usually normal and the perip heral white blood cell count is normal. In approximately one-third of cases, the disease is associated with a wide variety of congenital ano malies and malformations(3-7). Most cases are sporadic, but 10-20% of them follow a recessive or a dominant inheritance pattern(5). A female with DBA and a chromosomal translocation involving chromosome 19q was recently identified(8). We undertook a linkage analysis with chromoso me 19 markers in multiplex DBA families of Swedish, French, Dutch, Ara bic and Italian origin. Significant linkage to chromosome 19q13 was es tablished for dominant and recessive inherited DBA with a peak rod sco re at D19S197 (Z(max)=7.08, theta=0.00). Within this region, a submicr oscopic de novo deletion of 3.3 Mb was identified in a patient with DB A. The deletion coincides with the translocation break-point and, toge ther with key recombinations, restricts the DBA gene to a 1.8-Mb regio n. The results suggest that, despite its clinical heterogeneity, DBA i s genetically homogeneous for a gene in 19q13.