title: Does the Novel KLF1 Gene Mutation Lead to a Delay in Fetal Hemoglobin Switch?
abstract: The Kruppel-like factor 1 (KLF1) gene is an essential transcription factor that is required for the proper maturation of the erythroid cells. Recent studies have reported that KLF1 variations are associated with increased fetal hemoglobin (HbF) levels. Here we report a novel KLF1 gene variation codon 211 A→G (c.632 A>G) in a family who was referred for hemoglobinopathy screening. Both parents were classical β-thalassemia trait (mother: HbA24.1%, HbF 8.6%; father: HbA25.5%, HbF 0.6%) codon 15 G→A heterozygous, and the child was β-thalassemia homozygous. Because the mother showed a high HbF level, the genetic determinants for raised HbF were screened. We detected a novel KLF1 gene variant in the mother and the child in the heterozygous state. The co-inheritance of this novel KLF1 variant might have increased the HbF levels in the mother and may have ameliorated the clinical manifestations of the 6-year-old untransfused β-thalassemia homozygous child. Identification of KLF1 gene variants may act as a novel target for increasing HbF levels in patients with β-hemoglobinopathies.
authors.affiliation: Department of Haematogenetics, National Institute of Immunohaematology (ICMR), Parel, Mumbai, India.
authors.forename: Priya
authors.initials: P
authors.lastname: Hariharan
authors.affiliation: Department of Haematogenetics, National Institute of Immunohaematology (ICMR), Parel, Mumbai, India.
authors.forename: Manju
authors.initials: M
authors.lastname: Gorivale
authors.affiliation: Department of Haematogenetics, National Institute of Immunohaematology (ICMR), Parel, Mumbai, India.
authors.forename: Roshan
authors.initials: R
authors.lastname: Colah
authors.affiliation: Blood Bank, Surat Raktadan Kendra & Research Centre, Surat, Gujarat, India.
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
authors.affiliation: Department of Haematogenetics, National Institute of Immunohaematology (ICMR), Parel, Mumbai, India.
authors.forename: Anita
authors.initials: A
authors.lastname: Nadkarni
mesh_terms: D000328:Adult; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005319:Fetal Hemoglobin / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*
chemical_list: D051741:Kruppel-Like Transcription Factors; C080774:erythroid Kruppel-like factor; D005319:Fetal Hemoglobin
keywords: India; KLF1 mutation; raised HbF