Common fetal hemoglobin variants in Lebanese patients bearing the codon 29 beta gene mutation associated with different thalassemia phenotypes

Valentina Brancaleoni, Hassan M. Moukhadder, Dario Consonni, Suzanne Koussa, Elena Di Pierro, Maria Domenica Cappellini, Ali Taher

Research output: Contribution to journalArticle

Abstract

Beta-thalassemia can present with a wide spectrum of phenotypes determined by the coinheritance of α-thalassemia, hereditary persistence of fetal hemoglobin, and polymorphic variants in the BCL11A, HMIP, and HBB clusters. The codon 29 (cd29) mutation in the beta gene has been associated with a broad diversity of thalassemia phenotypes, possibly through genetic modifiers determining the genotype-phenotype relationship. In this study, we evaluated the effect of 10 single nucleotide polymorphisms (SNPs) on β-thalassemia severity in a group of 21 Lebanese patients bearing the cd29 mutation. Hematological parameters and clinical characteristics were evaluated according to transfusion dependence. The proportions and absolute concentrations of HbF were found to be higher in non-transfusion-dependent (NTD) patients than in transfusion-dependent (TD) ones. Iron parameters were found to be higher in TD patients. The SNPs that were evaluated included the XmnI-158 polymorphism in the HBG gene and SNPs in the BCL11A and HMIP loci. It was noted that individuals homozygous or heterozygous for the effect allele in the BCL11A and HMIP SNPs had higher HbF levels, lower ferritin concentrations, and lower liver iron content and were less likely to be transfusion dependent. Our results showed that HbF production variants may have an important impact on the severity of β-thalassemia, which might provide a severity prediction tool that can help in the anticipation of patients’ phenotypes and therefore in future therapeutic decision making.

Original languageEnglish
Pages (from-to)833-840
JournalAnnals of Hematology
Volume98
Issue number4
DOIs
Publication statusPublished - 2019

Fingerprint

Fetal Hemoglobin
Thalassemia
Codon
Single Nucleotide Polymorphism
Phenotype
Mutation
Genes
Iron
beta-Thalassemia
Ferritins
Decision Making
Alleles
Genotype
Liver
Therapeutics

Keywords

  • Fetal hemoglobin
  • Phenotype
  • Single nucleotide polymorphisms
  • Thalassemia
  • Transfusion

ASJC Scopus subject areas

  • Hematology

Cite this

@article{f73115505b9f43c98ddb23dd0c49c67a,
title = "Common fetal hemoglobin variants in Lebanese patients bearing the codon 29 beta gene mutation associated with different thalassemia phenotypes",
abstract = "Beta-thalassemia can present with a wide spectrum of phenotypes determined by the coinheritance of α-thalassemia, hereditary persistence of fetal hemoglobin, and polymorphic variants in the BCL11A, HMIP, and HBB clusters. The codon 29 (cd29) mutation in the beta gene has been associated with a broad diversity of thalassemia phenotypes, possibly through genetic modifiers determining the genotype-phenotype relationship. In this study, we evaluated the effect of 10 single nucleotide polymorphisms (SNPs) on β-thalassemia severity in a group of 21 Lebanese patients bearing the cd29 mutation. Hematological parameters and clinical characteristics were evaluated according to transfusion dependence. The proportions and absolute concentrations of HbF were found to be higher in non-transfusion-dependent (NTD) patients than in transfusion-dependent (TD) ones. Iron parameters were found to be higher in TD patients. The SNPs that were evaluated included the XmnI-158 polymorphism in the HBG gene and SNPs in the BCL11A and HMIP loci. It was noted that individuals homozygous or heterozygous for the effect allele in the BCL11A and HMIP SNPs had higher HbF levels, lower ferritin concentrations, and lower liver iron content and were less likely to be transfusion dependent. Our results showed that HbF production variants may have an important impact on the severity of β-thalassemia, which might provide a severity prediction tool that can help in the anticipation of patients’ phenotypes and therefore in future therapeutic decision making.",
keywords = "Fetal hemoglobin, Phenotype, Single nucleotide polymorphisms, Thalassemia, Transfusion",
author = "Valentina Brancaleoni and Moukhadder, {Hassan M.} and Dario Consonni and Suzanne Koussa and {Di Pierro}, Elena and Cappellini, {Maria Domenica} and Ali Taher",
year = "2019",
doi = "10.1007/s00277-018-3567-3",
language = "English",
volume = "98",
pages = "833--840",
journal = "Annals of Hematology",
issn = "0939-5555",
publisher = "Springer Verlag",
number = "4",

}

TY - JOUR

T1 - Common fetal hemoglobin variants in Lebanese patients bearing the codon 29 beta gene mutation associated with different thalassemia phenotypes

AU - Brancaleoni, Valentina

AU - Moukhadder, Hassan M.

AU - Consonni, Dario

AU - Koussa, Suzanne

AU - Di Pierro, Elena

AU - Cappellini, Maria Domenica

AU - Taher, Ali

PY - 2019

Y1 - 2019

N2 - Beta-thalassemia can present with a wide spectrum of phenotypes determined by the coinheritance of α-thalassemia, hereditary persistence of fetal hemoglobin, and polymorphic variants in the BCL11A, HMIP, and HBB clusters. The codon 29 (cd29) mutation in the beta gene has been associated with a broad diversity of thalassemia phenotypes, possibly through genetic modifiers determining the genotype-phenotype relationship. In this study, we evaluated the effect of 10 single nucleotide polymorphisms (SNPs) on β-thalassemia severity in a group of 21 Lebanese patients bearing the cd29 mutation. Hematological parameters and clinical characteristics were evaluated according to transfusion dependence. The proportions and absolute concentrations of HbF were found to be higher in non-transfusion-dependent (NTD) patients than in transfusion-dependent (TD) ones. Iron parameters were found to be higher in TD patients. The SNPs that were evaluated included the XmnI-158 polymorphism in the HBG gene and SNPs in the BCL11A and HMIP loci. It was noted that individuals homozygous or heterozygous for the effect allele in the BCL11A and HMIP SNPs had higher HbF levels, lower ferritin concentrations, and lower liver iron content and were less likely to be transfusion dependent. Our results showed that HbF production variants may have an important impact on the severity of β-thalassemia, which might provide a severity prediction tool that can help in the anticipation of patients’ phenotypes and therefore in future therapeutic decision making.

AB - Beta-thalassemia can present with a wide spectrum of phenotypes determined by the coinheritance of α-thalassemia, hereditary persistence of fetal hemoglobin, and polymorphic variants in the BCL11A, HMIP, and HBB clusters. The codon 29 (cd29) mutation in the beta gene has been associated with a broad diversity of thalassemia phenotypes, possibly through genetic modifiers determining the genotype-phenotype relationship. In this study, we evaluated the effect of 10 single nucleotide polymorphisms (SNPs) on β-thalassemia severity in a group of 21 Lebanese patients bearing the cd29 mutation. Hematological parameters and clinical characteristics were evaluated according to transfusion dependence. The proportions and absolute concentrations of HbF were found to be higher in non-transfusion-dependent (NTD) patients than in transfusion-dependent (TD) ones. Iron parameters were found to be higher in TD patients. The SNPs that were evaluated included the XmnI-158 polymorphism in the HBG gene and SNPs in the BCL11A and HMIP loci. It was noted that individuals homozygous or heterozygous for the effect allele in the BCL11A and HMIP SNPs had higher HbF levels, lower ferritin concentrations, and lower liver iron content and were less likely to be transfusion dependent. Our results showed that HbF production variants may have an important impact on the severity of β-thalassemia, which might provide a severity prediction tool that can help in the anticipation of patients’ phenotypes and therefore in future therapeutic decision making.

KW - Fetal hemoglobin

KW - Phenotype

KW - Single nucleotide polymorphisms

KW - Thalassemia

KW - Transfusion

UR - http://www.scopus.com/inward/record.url?scp=85057841092&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85057841092&partnerID=8YFLogxK

U2 - 10.1007/s00277-018-3567-3

DO - 10.1007/s00277-018-3567-3

M3 - Article

AN - SCOPUS:85057841092

VL - 98

SP - 833

EP - 840

JO - Annals of Hematology

JF - Annals of Hematology

SN - 0939-5555

IS - 4

ER -