Cargando…
The molecular basis of beta-thalassemia intermedia in southern China: genotypic heterogeneity and phenotypic diversity
BACKGROUND: The clinical syndrome of thalassemia intermedia (TI) results from the β-globin genotypes in combination with factors to produce fetal haemoglobin (HbF) and/or co-inheritance of α-thalassemia. However, very little is currently known of the molecular basis of Chinese TI patients. METHODS:...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2010
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845123/ https://www.ncbi.nlm.nih.gov/pubmed/20181291 http://dx.doi.org/10.1186/1471-2350-11-31 |
_version_ | 1782179381412626432 |
---|---|
author | Chen, Wanqun Zhang, Xinhua Shang, Xuan Cai, Ren Li, Liyan Zhou, Tianhong Sun, Manna Xiong, Fu Xu, Xiangmin |
author_facet | Chen, Wanqun Zhang, Xinhua Shang, Xuan Cai, Ren Li, Liyan Zhou, Tianhong Sun, Manna Xiong, Fu Xu, Xiangmin |
author_sort | Chen, Wanqun |
collection | PubMed |
description | BACKGROUND: The clinical syndrome of thalassemia intermedia (TI) results from the β-globin genotypes in combination with factors to produce fetal haemoglobin (HbF) and/or co-inheritance of α-thalassemia. However, very little is currently known of the molecular basis of Chinese TI patients. METHODS: We systematically analyzed and characterized β-globin genotypes, α-thalassemia determinants, and known primary genetic modifiers linked to the production of HbF and the aggravation of α/β imbalance in 117 Chinese TI patients. Genotype-phenotype correlations were analyzed based on retrospective clinical observations. RESULTS: A total of 117 TI patients were divided into two major groups, namely heterozygous β-thalassemia (n = 20) in which 14 were characterized as having a mild TI with the Hb levels of 68-95 g/L except for five co-inherited ααα(anti-3.7 )triplication and one carried a dominant mutation; and β-thalassemia homozygotes or compound heterozygotes for β-thalassemia and other β-globin defects in which the β(+)-thalassemia mutation was the most common (49/97), hemoglobin E (HbE) variants was second (27/97), and deletional hereditary persistence of fetal hemoglobin (HPFH) or δβ-thalassemia was third (11/97). Two novel mutations, Term CD+32(A→C) and Cap+39(C→T), have been detected. CONCLUSIONS: Chinese TI patients showed considerable heterogeneity, both phenotypically and genotypically. The clinical outcomes of our TI patients were mostly explained by the genotypes linked to the β- and α-globin gene cluster. However, for a group of 14 patients (13 β(0)/β(N )and 1 β(+)/β(N)) with known heterozygous mutations of β-thalassemia and three with homozygous β-thalassemia (β(0)/β(0)), the existence of other causative genetic determinants is remaining to be molecularly defined. |
format | Text |
id | pubmed-2845123 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-28451232010-03-26 The molecular basis of beta-thalassemia intermedia in southern China: genotypic heterogeneity and phenotypic diversity Chen, Wanqun Zhang, Xinhua Shang, Xuan Cai, Ren Li, Liyan Zhou, Tianhong Sun, Manna Xiong, Fu Xu, Xiangmin BMC Med Genet Research Article BACKGROUND: The clinical syndrome of thalassemia intermedia (TI) results from the β-globin genotypes in combination with factors to produce fetal haemoglobin (HbF) and/or co-inheritance of α-thalassemia. However, very little is currently known of the molecular basis of Chinese TI patients. METHODS: We systematically analyzed and characterized β-globin genotypes, α-thalassemia determinants, and known primary genetic modifiers linked to the production of HbF and the aggravation of α/β imbalance in 117 Chinese TI patients. Genotype-phenotype correlations were analyzed based on retrospective clinical observations. RESULTS: A total of 117 TI patients were divided into two major groups, namely heterozygous β-thalassemia (n = 20) in which 14 were characterized as having a mild TI with the Hb levels of 68-95 g/L except for five co-inherited ααα(anti-3.7 )triplication and one carried a dominant mutation; and β-thalassemia homozygotes or compound heterozygotes for β-thalassemia and other β-globin defects in which the β(+)-thalassemia mutation was the most common (49/97), hemoglobin E (HbE) variants was second (27/97), and deletional hereditary persistence of fetal hemoglobin (HPFH) or δβ-thalassemia was third (11/97). Two novel mutations, Term CD+32(A→C) and Cap+39(C→T), have been detected. CONCLUSIONS: Chinese TI patients showed considerable heterogeneity, both phenotypically and genotypically. The clinical outcomes of our TI patients were mostly explained by the genotypes linked to the β- and α-globin gene cluster. However, for a group of 14 patients (13 β(0)/β(N )and 1 β(+)/β(N)) with known heterozygous mutations of β-thalassemia and three with homozygous β-thalassemia (β(0)/β(0)), the existence of other causative genetic determinants is remaining to be molecularly defined. BioMed Central 2010-02-25 /pmc/articles/PMC2845123/ /pubmed/20181291 http://dx.doi.org/10.1186/1471-2350-11-31 Text en Copyright ©2010 Chen et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Chen, Wanqun Zhang, Xinhua Shang, Xuan Cai, Ren Li, Liyan Zhou, Tianhong Sun, Manna Xiong, Fu Xu, Xiangmin The molecular basis of beta-thalassemia intermedia in southern China: genotypic heterogeneity and phenotypic diversity |
title | The molecular basis of beta-thalassemia intermedia in southern China: genotypic heterogeneity and phenotypic diversity |
title_full | The molecular basis of beta-thalassemia intermedia in southern China: genotypic heterogeneity and phenotypic diversity |
title_fullStr | The molecular basis of beta-thalassemia intermedia in southern China: genotypic heterogeneity and phenotypic diversity |
title_full_unstemmed | The molecular basis of beta-thalassemia intermedia in southern China: genotypic heterogeneity and phenotypic diversity |
title_short | The molecular basis of beta-thalassemia intermedia in southern China: genotypic heterogeneity and phenotypic diversity |
title_sort | molecular basis of beta-thalassemia intermedia in southern china: genotypic heterogeneity and phenotypic diversity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845123/ https://www.ncbi.nlm.nih.gov/pubmed/20181291 http://dx.doi.org/10.1186/1471-2350-11-31 |
work_keys_str_mv | AT chenwanqun themolecularbasisofbetathalassemiaintermediainsouthernchinagenotypicheterogeneityandphenotypicdiversity AT zhangxinhua themolecularbasisofbetathalassemiaintermediainsouthernchinagenotypicheterogeneityandphenotypicdiversity AT shangxuan themolecularbasisofbetathalassemiaintermediainsouthernchinagenotypicheterogeneityandphenotypicdiversity AT cairen themolecularbasisofbetathalassemiaintermediainsouthernchinagenotypicheterogeneityandphenotypicdiversity AT liliyan themolecularbasisofbetathalassemiaintermediainsouthernchinagenotypicheterogeneityandphenotypicdiversity AT zhoutianhong themolecularbasisofbetathalassemiaintermediainsouthernchinagenotypicheterogeneityandphenotypicdiversity AT sunmanna themolecularbasisofbetathalassemiaintermediainsouthernchinagenotypicheterogeneityandphenotypicdiversity AT xiongfu themolecularbasisofbetathalassemiaintermediainsouthernchinagenotypicheterogeneityandphenotypicdiversity AT xuxiangmin themolecularbasisofbetathalassemiaintermediainsouthernchinagenotypicheterogeneityandphenotypicdiversity AT chenwanqun molecularbasisofbetathalassemiaintermediainsouthernchinagenotypicheterogeneityandphenotypicdiversity AT zhangxinhua molecularbasisofbetathalassemiaintermediainsouthernchinagenotypicheterogeneityandphenotypicdiversity AT shangxuan molecularbasisofbetathalassemiaintermediainsouthernchinagenotypicheterogeneityandphenotypicdiversity AT cairen molecularbasisofbetathalassemiaintermediainsouthernchinagenotypicheterogeneityandphenotypicdiversity AT liliyan molecularbasisofbetathalassemiaintermediainsouthernchinagenotypicheterogeneityandphenotypicdiversity AT zhoutianhong molecularbasisofbetathalassemiaintermediainsouthernchinagenotypicheterogeneityandphenotypicdiversity AT sunmanna molecularbasisofbetathalassemiaintermediainsouthernchinagenotypicheterogeneityandphenotypicdiversity AT xiongfu molecularbasisofbetathalassemiaintermediainsouthernchinagenotypicheterogeneityandphenotypicdiversity AT xuxiangmin molecularbasisofbetathalassemiaintermediainsouthernchinagenotypicheterogeneityandphenotypicdiversity |