Molecular characterization of a Portuguese patient with Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS) a rare autosomal recessive disorder described first time 1964 (1), is characterized by the association of exocrine pancreatic and bone marrow dysfunction. Other systemic findings (skeletal, liver and psychomotor) or problems secondary to bone marrow dysfunction may also be detected (1–4). Intermittent or persistent neutropenia is the most common hematologic finding, but anemia and thrombocytopenia are present in approximately 40% of the patients (1–4). In 2002, fine mapping identified the locus for SDS in band 7q11. More recently Boocock et al. (5) identified 18 positional candidate genes in this locus and examined eight of them for occurrence SDS-associated changes. They found alterations only in a previously uncharacterised gene. This gene, designated SBDS (ShwachmanBodian-Diamond syndrome), is composed of five exons spanning 7.9Kb. The authors also described a pseudogene (SBDSP) with 97% homology to SBDS (5). Only two reports have described mutations in the SBDS gene. The original article described 14 different mutations found in 158 SDS families, mostly of European ancestry. The majority of SBDS mutations were found to occur within a 240-bp region around exon 2 and resulted from gene conversion as the result of recombination with the pseudogene (5). In the other report, mutations were identified in four patients; two recurring mutations and three novel changes were found (6). We describe a Portuguese patient with SDS found to be compound heterozygous for two previously described mutations (183–184TA.CT + 201A.G and 258+2T.C). CASE REPORT