GENETIC-ANALYSIS OF FAMILIAL MYELODYSPLASTIC SYNDROME - ABSENCE OF LINKAGE TO CHROMOSOMES 5Q31 AND 7Q22

Myelodysplastic syndrome (MDS) is a hematological disorder that occurs primarily in the elderly as an acquired, sporadic disease. Familial c ases of MDS are rare. We have identified a kindred with three affected individuals, with early age of onset, suggesting a possible inherited predisposition to this disease. Using a molecular genetic approach, w e examined whether bands 5q31 or 7q22 or both, the chromosomal regions most frequently associated with sporadic MDS, are involved in familia l expression of MDS in this pedigree. Linkage analysis using polymorph ic microsatellite DNA markers demonstrated that neither 5q31 nor 7q22 cosegregated with MDS in this family. There was no history of common e nvironmental or occupational exposure among family members with MDS. I n addition, analysis of polymorphisms at two loci [glutathione S-trans ferase T1 and M1 (GSTT1 and GSTM1)] involved in carcinogen detoxificat ion and associated with cancer susceptibility, including increased ris k for MDS, showed no evidence for enhanced sensitivity to environmenta l carcinogens in affected family members. Taken together, our findings suggest that (1) there is an inherited predisposition to MDS in this kindred; and (2) genes at 5q31 and 7q22, the regions most commonly ass ociated with sporadic MDS, are excluded from a causal role in this fam ily's disease. (C) Elsevier Science Inc., 1998