Isochromosome (7)(q10) in Shwachman syndrome without MDS/AML and role of chromosome 7 anomalies in myeloproliferative disorders

Shwachman syndrome (SS) is an autosomal recessive disorder in which bone ma rrow dysfunction is observed, with development of myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML) in up to one third of the cases. I nconclusive data are available as to increased chromosome breakage in SS, w hile chromosome 7 anomalies, and often an isochromosome (7)(q10), are frequ ent in cases with MDS/AML. We report on the consistent presence of an i(7)( q10) in the bone marrow and blood lymphocytes in one of two sisters affecte d with SS without any clinical or cytological signs of MDS/AML. Th us, this patient was either a case of constitutional mosaicism for the i(7)(q10), o r this had to be acquired in a nondysplastic and non-neoplastic marrow clon e. DNA polymorphism analysis demonstrated the paternal origin of the i(7q). We postulate that the SS mutation acts as a mutator gene, and causes karyo type instability; abnormal clones would thus arise in the marrow, and chrom osome 7 anomalies, i(7q) in particular, will in turn lead to MDS/AML. If th is interpretation is correct, it would be also an indication to consider ch romosome 7 anomalies in general, out of SS, as primary changes in MDS/AML p athogenesis. (C) 2000 Elsevier Science inc. All rights reserved.