Shwachman-Diamond syndrome with exocrine pancreatic dysfunction and bone marrow failure maps to the centromeric region of chromosome 7

Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder charact erized by exocrine pancreatic insufficiency and hematologic and skeletal ab normalities. A genomewide scan of families with SDS was terminated at simil ar to 50% completion, with the identification of chromosome 7 markers that showed linkage with the disease. Finer mapping revealed significant linkage across a broad interval that included the centromere. The maximum two-poin t LOD score was 8.7, with D7S473, at a recombination fraction of 0. The max imum multipoint LOD score was 10, in the interval between D7S499 and D7S482 (5.4 cM on the female map and 0 cM on the male map), a region delimited by recombinant events detected in affected children. Evidence from all 15 of the multiplex families analyzed provided support for the linkage, consisten t with a single locus for SDS. However, the presence of several different m utations is suggested by the heterogeneity of disease-associated haplotypes in the candidate region.