title: Ten novel mutations in the erythroid transcription factor KLF1 gene associated with increased fetal hemoglobin levels in adults.
abstract: We investigated whether mutations in the KLF1 gene are associated with increased Hb F levels in ethnically diverse patients referred to our laboratory for hemoglobinopathy investigation. Functionally effective KLF1 mutations were identified in 11 out of 131 adult samples with an elevated Hb F level (1.5-25.0%). Eleven different mutations were identified, 9 of which were previously unreported. KLF1 mutations were not identified in a matched cohort of 121 samples with normal Hb F levels (<1.0%). A further novel KLF1 mutation was also found in a sickle cell disease patient with a Hb F level of 20.3% who had a particularly mild phenotype. Our results indicate KLF1 mutations could make a significant contribution to Hb F variance in malarial regions where hemogobinopathies are common. All the mutations identified were heterozygous providing further in vivo evidence that a single altered KLF1 allele is sufficient to increase Hb F levels.
authors.affiliation: National Haemoglobinopathy Reference Laboratory, Oxford Biomedical Research Centre-Haematology Molecular Diagnostic Service, John Radcliffe Hospital, Oxford, UK.
authors.forename: Alice E
authors.initials: AE
authors.lastname: Gallienne
authors.forename: Hélène M P
authors.initials: HM
authors.lastname: Dréau
authors.forename: Anna
authors.initials: A
authors.lastname: Schuh
authors.forename: John M
authors.initials: JM
authors.lastname: Old
authors.forename: Shirley
authors.initials: S
authors.lastname: Henderson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000755:Anemia, Sickle Cell / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005319:Fetal Hemoglobin / Q000378:metabolism*; D023061:Gene Order; D056726:Genetic Association Studies; D005838:Genotype; D006453:Hemoglobinopathies / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007223:Infant; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D051741:Kruppel-Like Transcription Factors; C080774:erythroid Kruppel-like factor; D005319:Fetal Hemoglobin
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