Abstract • 95

Diamond-Blackfan anemia (DBA) a constitutional disease due to a specific maturation arrest of the erythroid lineage, is heterogeneous in terms of associated malformations, mode of inheritance and therapeutic outcome. While most forms appear to be sporadic, some family pedigrees evidence a dominant mode of inheritance or a consaguinity. During the years 1995-1999 major advances have been achieved in the field of genetics of DBA, resulting from the works of the group of N. Dähl (Uppsala, Sweden) and of a close joint collaboration of several European groups. The occurrence of a balanced X/19 translocation in a DBA affected female suggested that the phenotype could be the result of a haplo insufficiency for a disrupted gene on chromosome 19q. 19q directed linkage study of families with inherited DBA, using polymorphic microsatellite markers, and the finding of several de novo microdeletions led to further define the DBA locus on chromosome 19q13.2 and to narrow the space to a 1Mb region including several candidate genes. At this point new facts emerged:

  1. 1

    Linkage studies of other DBA families, both in Europe and US failed to show a constant linkage with the 19q DBA locus, shedding new light on the genetic heterogeneity of the disease and opening the search for one or several other DBA loci.

  2. 2

    Cautious reassessment of 19q linkage analysis in some families with DBA affected individuals showed that the linkage, when found, could concern DBA affected individuals but also healthy relatives who exhibited high erythrocyte adenosine deaminase levels, thus providing a reliable tool, albeit of unknown pathophysiological significance, for refining family studies.

  3. 3

    More recently a candidate gene has been clearly incriminated, which opens a new and fascinating chapter for pathophysiological speculations and new experiments.