title: Krüppel-like factor 1 mutations and expression of hemoglobins F and A2 in homozygous hemoglobin E syndrome.
abstract: The basis for variability of hemoglobin (Hb) F in homozygous Hb E disease is not well understood. We have examined multiple mutations of the Krüppel-like factor 1 (KLF1) gene; an erythroid specific transcription factor and determined their associations with Hbs F and A2 expression in homozygous Hb E. Four KLF1 mutations including G176AfsX179, T334R, R238H, and -154 (C-T) were screened using specific PCR assays on 461 subjects with homozygous Hb E and 100 normal controls. None of these four mutations were observed in 100 normal controls. Among 461 subjects with homozygous Hb E, 306 had high (≥5 %) and 155 had low (<5 %) Hb F. DNA analysis identified the KLF1 mutations in 35 cases of the former group with high Hb F, including the G176AfsX179 mutation (17/306 = 5.6 %), T334R mutation (9/306 = 2.9 %), -154 (C-T) mutation (7/306 = 2.3 %), and R328H mutation (2/306 = 0.7 %). Only two subjects in the latter group with low Hb F carried the G176AfsX179 and -154 (C-T) mutations. Significant higher Hb A2 level was observed in those of homozygous Hb E with the G176AfsX179 mutation as compared to those without KLF1 mutations. These results indicate that KLF1 is among the genetic factors associated with increased Hbs F and A2, and in combination with other factors could explain the variabilities of these Hb expression in Hb E syndrome.
authors.affiliation: Biomedical Science Program, Graduate School, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Wanicha
authors.initials: W
authors.lastname: Tepakhan
authors.forename: Supawadee
authors.initials: S
authors.lastname: Yamsri
authors.forename: Goonnapa
authors.initials: G
authors.lastname: Fucharoen
authors.forename: Kanokwan
authors.initials: K
authors.lastname: Sanchaisuriya
authors.forename: Supan
authors.initials: S
authors.lastname: Fucharoen
mesh_terms: D005319:Fetal Hemoglobin / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D006443:Hemoglobin A2 / Q000096:biosynthesis / Q000235:genetics*; D006446:Hemoglobin E / Q000096:biosynthesis / Q000235:genetics*; D006453:Hemoglobinopathies / Q000175:diagnosis / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D013577:Syndrome
chemical_list: D051741:Kruppel-Like Transcription Factors; C080774:erythroid Kruppel-like factor; D006443:Hemoglobin A2; D006446:Hemoglobin E; D005319:Fetal Hemoglobin