title: Changes in hematological parameters in α-thalassemia individuals co-inherited with erythroid Krüppel-like factor mutations.
abstract: Phenotypic variations in α-thalassemia mainly depend on the defective α-globin gene number. Genetic modifiers of the phenotype of Hemoglobin H (HbH) disease were poorly reported, apart from β-thalassemia allele that was identified ameliorating the severity of α-thalassemia. Because erythroid Krüppel-like factor (KLF1) mutations can modulate the red blood phenotype, we evaluated its effect on the α-thalassemia phenotype. Overall, we identified 72 subjects with five different KLF1 heterozygous mutations in 1468 individuals, including 65 out of 432 α-thalassemia carriers with fetal hemoglobin (HbF) levels ≥1%, 0 out of 310 carriers with HbF levels <1% and 7 out of 726 HbH disease patients. We firstly established the link between KLF1 mutations and relatively elevated hemoglobin A2 (HbA2 ) and HbF levels, along with lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) values in a group of α-thalassemia carriers. However, we concluded that KLF1 mutations were not significantly linked to HbH disease severity. On the basis of HBA or HBB genotype and gender, clinical severity of patients with HbH disease was correctly predicted in 73.3% cases. It may improve the screening and diagnostic assessment of α-thalassemia.
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, P.R.China.
authors.forename: L-H
authors.initials: LH
authors.lastname: Yu
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, P.R.China.
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Birth Health and Heredity, Liuzhou Women and Children Care Hospital, Liuzhou, Guangxi, P.R.China.
authors.forename: R
authors.initials: R
authors.lastname: Cai
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, P.R.China.
authors.forename: X
authors.initials: X
authors.lastname: Shang
authors.affiliation: Department of Hematology, 303rd Hospital of the People's Liberation Army, Nanning, Guangxi, P.R.China.
authors.forename: X-H
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, P.R.China.
authors.forename: X-X
authors.initials: XX
authors.lastname: Ma
authors.affiliation: Laboratory of Medical Genetics, Maternal and Child Health Care Hospital of Qinzhou, Qinzhou, Guangxi, P.R.China.
authors.forename: S-H
authors.initials: SH
authors.lastname: Yan
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, P.R.China.
authors.forename: P
authors.initials: P
authors.lastname: Fang
authors.affiliation: Prenatal Diagnostic Center, Guangxi Zhuang Autonomous Region Women and Children Care Hospital, Nanning, Guangxi, P.R.China.
authors.forename: C-G
authors.initials: CG
authors.lastname: Zheng
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, P.R.China.
authors.forename: X-F
authors.initials: XF
authors.lastname: Wei
authors.affiliation: Prenatal Diagnosis Center, Maternal and Child Health Hospital, Dongguan, Guangdong, P.R.China.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Clinical Laboratory, Yunnan Women and Children Care Hospital, Kunming, Yunnan, P.R.China.
authors.forename: T-B
authors.initials: TB
authors.lastname: Zhou
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, P.R.China.
authors.forename: X-M
authors.initials: XM
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004909:Erythrocyte Indices / Q000235:genetics*; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis; D006443:Hemoglobin A2 / Q000032:analysis; D006801:Humans; D007223:Infant; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D055815:Young Adult; D055542:alpha-Globins / Q000235:genetics; D017085:alpha-Thalassemia / Q000097:blood / Q000235:genetics*
chemical_list: D051741:Kruppel-Like Transcription Factors; D055542:alpha-Globins; C080774:erythroid Kruppel-like factor; D006443:Hemoglobin A2; D005319:Fetal Hemoglobin
keywords: clinical severity; erythroid Krüppel-like factor; genetic modifier; red blood phenotype; α-thalassemia