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Hemochromatosis‐associated gene mutations in patients with myelodysplastic syndromes with refractory anemia with ringed sideroblasts
Author(s) -
Nearman Zachary P.,
Szpurka Hadrian,
Serio Bianca,
Warshawksy Ilka,
Theil Karl,
Lichtin Alan,
Sekeres Mikkael A.,
Maciejewski Jaroslaw P.
Publication year - 2007
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.20995
Subject(s) - myelodysplastic syndromes , medicine , hemochromatosis , hereditary hemochromatosis , gastroenterology , thrombocytosis , allele frequency , genotype , population , biology , genetics , gene , bone marrow , platelet , environmental health
We observed increased ferritin levels in newly diagnosed MDS‐RARS patients without transfusional iron‐overload. Hence, we hypothesized RARS patients may harbor hemochromatosis‐related mutations, which could contribute to the pathophysiology of this myelodysplastic syndromes (MDS) subset. We studied a cohort of 140 MDS patients: 42 with RARS, 10 with increased ringed sideroblasts, and 96 with other forms of MDS (43 RA, 27 RAEB, 17 RAEB‐T, 8 MDS/MPD, 1 CMML). Patients were genotyped using restriction fragment length polymorphism, designed to detect C282Y and H63D mutations of the HFE gene. We found significantly higher frequency of heterozygosity for C282Y mutation in RARS patients compared with a large control population of matched race individuals (21 vs. 9.8% in controls, P = 0.03); H63D genotype was not significantly increased. Frequency of HFE variation in other MDS subtypes failed to differ significantly from controls. Within this group, we included patients with a rare form of MDS, provisionally subclassified by WHO as RARS with thrombocytosis (RARSt). 10/14 RARSt patients were carriers of either C282Y or H63D allele significantly increased compared with the combined prevalence in a healthy population (71 vs. 33%, P < 0.01). We found expected distribution of mutant HFE alleles in patients with other forms of MDS (9.1 vs. 9.8%, P = 0.82). Increased prevalence of HFE gene mutations is not a generalized feature of MDS, but some subgroups of MDS, especially those characterized by excessive accumulation of ringed sideroblasts, exhibit C282Y mutations at a higher frequency than in other forms of MDS and healthy controls. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.