Genotype-phenotype association analysis identifies the role of α globin genes in modulating disease severity of β thalassaemia intermedia in Sri Lanka

Abstract β thalassaemia intermedia (βTI) are a heterogeneous group of disorders known to be extremely phenotypically diverse. This group is more complex to manage as no definitive treatment guidelines exist unlike for β thalassaemia major (βTM). There are only a few studies looking at genotype pheno...

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Autores principales:	Shiromi Perera, Angela Allen, Ishari Silva, Menaka Hapugoda, M. Nirmali Wickramarathne, Indira Wijesiriwardena, Stephen Allen, David Rees, Dimitar G. Efremov, Christopher A. Fisher, David J. Weatherall, Anuja Premawardhena
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6778d9b209994bc0ba59c70f57f95b78
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spelling	oai:doaj.org-article:6778d9b209994bc0ba59c70f57f95b782021-12-02T15:08:32ZGenotype-phenotype association analysis identifies the role of α globin genes in modulating disease severity of β thalassaemia intermedia in Sri Lanka10.1038/s41598-019-46674-y2045-2322https://doaj.org/article/6778d9b209994bc0ba59c70f57f95b782019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-46674-yhttps://doaj.org/toc/2045-2322Abstract β thalassaemia intermedia (βTI) are a heterogeneous group of disorders known to be extremely phenotypically diverse. This group is more complex to manage as no definitive treatment guidelines exist unlike for β thalassaemia major (βTM). There are only a few studies looking at genotype phenotype associations of βTI outside the Mediterranean region. The reasons for the diverse clinical phenotype in βTI are unknown. We categorized fifty Sri Lankan patients diagnosed with βTI as mild, moderate or severe according to published criteria. DNA samples were genotyped for β thalassaemia mutations, α globin genotype and copy number and known genetic modifiers of haemoglobin F production. There were 26/50 (52.0%) in mild group and 12/50 (24.0%) each in moderate and sever categories. 18/26 (69.2%) classified as mild were β heterozygotes and 17/18 (94.4%) had excess α globin genes. 11/12 (91.6%) classified as moderate were β heterozygotes and 8/11 (72.2%) had excess α globin genes. In contrast, 8/12 (66.7%) classified as severe were β homozygotes and 7/8(87.5%) had α globin gene deletions. In Sri Lanka, co-inheritance of either excess α globin genes in β thalassaemia heterozygotes or α globin gene deletions in β thalassaemia homozygotes is a significant factor in modulating disease severity.Shiromi PereraAngela AllenIshari SilvaMenaka HapugodaM. Nirmali WickramarathneIndira WijesiriwardenaStephen AllenDavid ReesDimitar G. EfremovChristopher A. FisherDavid J. WeatherallAnuja PremawardhenaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-9 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shiromi Perera Angela Allen Ishari Silva Menaka Hapugoda M. Nirmali Wickramarathne Indira Wijesiriwardena Stephen Allen David Rees Dimitar G. Efremov Christopher A. Fisher David J. Weatherall Anuja Premawardhena Genotype-phenotype association analysis identifies the role of α globin genes in modulating disease severity of β thalassaemia intermedia in Sri Lanka
description	Abstract β thalassaemia intermedia (βTI) are a heterogeneous group of disorders known to be extremely phenotypically diverse. This group is more complex to manage as no definitive treatment guidelines exist unlike for β thalassaemia major (βTM). There are only a few studies looking at genotype phenotype associations of βTI outside the Mediterranean region. The reasons for the diverse clinical phenotype in βTI are unknown. We categorized fifty Sri Lankan patients diagnosed with βTI as mild, moderate or severe according to published criteria. DNA samples were genotyped for β thalassaemia mutations, α globin genotype and copy number and known genetic modifiers of haemoglobin F production. There were 26/50 (52.0%) in mild group and 12/50 (24.0%) each in moderate and sever categories. 18/26 (69.2%) classified as mild were β heterozygotes and 17/18 (94.4%) had excess α globin genes. 11/12 (91.6%) classified as moderate were β heterozygotes and 8/11 (72.2%) had excess α globin genes. In contrast, 8/12 (66.7%) classified as severe were β homozygotes and 7/8(87.5%) had α globin gene deletions. In Sri Lanka, co-inheritance of either excess α globin genes in β thalassaemia heterozygotes or α globin gene deletions in β thalassaemia homozygotes is a significant factor in modulating disease severity.
format	article
author	Shiromi Perera Angela Allen Ishari Silva Menaka Hapugoda M. Nirmali Wickramarathne Indira Wijesiriwardena Stephen Allen David Rees Dimitar G. Efremov Christopher A. Fisher David J. Weatherall Anuja Premawardhena
author_facet	Shiromi Perera Angela Allen Ishari Silva Menaka Hapugoda M. Nirmali Wickramarathne Indira Wijesiriwardena Stephen Allen David Rees Dimitar G. Efremov Christopher A. Fisher David J. Weatherall Anuja Premawardhena
author_sort	Shiromi Perera
title	Genotype-phenotype association analysis identifies the role of α globin genes in modulating disease severity of β thalassaemia intermedia in Sri Lanka
title_short	Genotype-phenotype association analysis identifies the role of α globin genes in modulating disease severity of β thalassaemia intermedia in Sri Lanka
title_full	Genotype-phenotype association analysis identifies the role of α globin genes in modulating disease severity of β thalassaemia intermedia in Sri Lanka
title_fullStr	Genotype-phenotype association analysis identifies the role of α globin genes in modulating disease severity of β thalassaemia intermedia in Sri Lanka
title_full_unstemmed	Genotype-phenotype association analysis identifies the role of α globin genes in modulating disease severity of β thalassaemia intermedia in Sri Lanka
title_sort	genotype-phenotype association analysis identifies the role of α globin genes in modulating disease severity of β thalassaemia intermedia in sri lanka
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/6778d9b209994bc0ba59c70f57f95b78
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Genotype-phenotype association analysis identifies the role of α globin genes in modulating disease severity of β thalassaemia intermedia in Sri Lanka

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