Further acatalasemia mutations in human patients from Hungary with diabetes and microcytic anemia

In blood, the hydrogen peroxide concentration is regulated by catalase. Decreased activity of catalase may lead to increased hydrogen peroxide concentration, which may contribute to the manifestation of age-related disease. The aim of this study is to examine association of decreased blood catalase activity and catalase exon mutations in patients (n = 617) with diabetes (n = 380), microcytic anemia (n = 58), beta-thalassemia (n = 43) and presbycusis (n = 136) and in controls (n = 295). Overall, 51 patients (8.3%) had less than half of normal blood catalase activity. Their genomic DNA was used for mutation screening of all exons and exon/intron boundaries with polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and PCR-heteroduplex analyses, and mutations were verified with nucleotide sequencing. Seven patients (type 2 diabetes (n = 3), gestational diabetes (n = 1), microcytic anemia (n = 2)) had four novel catalase exon mutations namely, c.106_107insC, p.G36Afs*5(n = 3, Hungarian type G1), c.379C>T, p.R127Y (n = 2, Hungarian type H1), c.390T>C, p.R129L, (n = 1, Hungarian type H2) and c.431A>T, p.N143V (n = 1, Hungarian type H3). In patients with decreased blood catalase, the incidence of acatalasemia mutations was significantly high (P < 0.0002) in microcytic anemia, type 2 and gestational diabetes. The four novel mutations were probably responsible for low blood catalase activity in 7/51 patients. In the remainder of the cases, other polymorphisms and epigenetic/regulatory factors may be involved.