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Glanzmann thrombasthenia in Pakistan: molecular analysis and identification of novel mutations

Glanzmann thrombasthenia (GT) is an inherited genetic disorder affecting platelets, which is characterized by spontaneous mucocutaneous bleeding and abnormally prolonged bleeding in response to injury or trauma. The underlying defect is failure of platelet aggregation due to qualitative and/or quant...

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Autores principales: Haghighi, A., Borhany, M., Ghazi, A., Edwards, N., Tabaksert, A., Fatima, N., Shamsi, T.S., Sayer, J.A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737203/
https://www.ncbi.nlm.nih.gov/pubmed/26096001
http://dx.doi.org/10.1111/cge.12622
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author Haghighi, A.
Borhany, M.
Ghazi, A.
Edwards, N.
Tabaksert, A.
Haghighi, A.
Fatima, N.
Shamsi, T.S.
Sayer, J.A.
author_facet Haghighi, A.
Borhany, M.
Ghazi, A.
Edwards, N.
Tabaksert, A.
Haghighi, A.
Fatima, N.
Shamsi, T.S.
Sayer, J.A.
author_sort Haghighi, A.
collection PubMed
description Glanzmann thrombasthenia (GT) is an inherited genetic disorder affecting platelets, which is characterized by spontaneous mucocutaneous bleeding and abnormally prolonged bleeding in response to injury or trauma. The underlying defect is failure of platelet aggregation due to qualitative and/or quantitative deficiency of platelet integrin αIIbβ3 resulting from molecular genetic defects in either ITGA2B or ITGB3. Here, we examine a Pakistani cohort of 15 patients with clinical symptoms of GT who underwent laboratory and molecular genetic analysis. In patients with a broad range of disease severity and age of presentation, we identified pathogenic mutations in ITGA2B in 11 patients from 8 different families, including 2 novel homozygous mutations and 1 novel heterozygous mutation. Mutations in ITGB3 were identified in 4 patients from 3 families, two of which were novel homozygous truncating mutations. A molecular genetic diagnosis was established in 11 families with GT, including 5 novel mutations extending the spectrum of mutations in this disease within a region of the world where little is known about the incidence of GT. Mutational analysis is a key component of a complete diagnosis of GT and allows appropriate management and screening of other family members to be performed.
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spelling pubmed-47372032016-02-11 Glanzmann thrombasthenia in Pakistan: molecular analysis and identification of novel mutations Haghighi, A. Borhany, M. Ghazi, A. Edwards, N. Tabaksert, A. Haghighi, A. Fatima, N. Shamsi, T.S. Sayer, J.A. Clin Genet Short Reports Glanzmann thrombasthenia (GT) is an inherited genetic disorder affecting platelets, which is characterized by spontaneous mucocutaneous bleeding and abnormally prolonged bleeding in response to injury or trauma. The underlying defect is failure of platelet aggregation due to qualitative and/or quantitative deficiency of platelet integrin αIIbβ3 resulting from molecular genetic defects in either ITGA2B or ITGB3. Here, we examine a Pakistani cohort of 15 patients with clinical symptoms of GT who underwent laboratory and molecular genetic analysis. In patients with a broad range of disease severity and age of presentation, we identified pathogenic mutations in ITGA2B in 11 patients from 8 different families, including 2 novel homozygous mutations and 1 novel heterozygous mutation. Mutations in ITGB3 were identified in 4 patients from 3 families, two of which were novel homozygous truncating mutations. A molecular genetic diagnosis was established in 11 families with GT, including 5 novel mutations extending the spectrum of mutations in this disease within a region of the world where little is known about the incidence of GT. Mutational analysis is a key component of a complete diagnosis of GT and allows appropriate management and screening of other family members to be performed. Blackwell Publishing Ltd 2015-07-15 2016-02 /pmc/articles/PMC4737203/ /pubmed/26096001 http://dx.doi.org/10.1111/cge.12622 Text en © 2015 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Reports
Haghighi, A.
Borhany, M.
Ghazi, A.
Edwards, N.
Tabaksert, A.
Haghighi, A.
Fatima, N.
Shamsi, T.S.
Sayer, J.A.
Glanzmann thrombasthenia in Pakistan: molecular analysis and identification of novel mutations
title Glanzmann thrombasthenia in Pakistan: molecular analysis and identification of novel mutations
title_full Glanzmann thrombasthenia in Pakistan: molecular analysis and identification of novel mutations
title_fullStr Glanzmann thrombasthenia in Pakistan: molecular analysis and identification of novel mutations
title_full_unstemmed Glanzmann thrombasthenia in Pakistan: molecular analysis and identification of novel mutations
title_short Glanzmann thrombasthenia in Pakistan: molecular analysis and identification of novel mutations
title_sort glanzmann thrombasthenia in pakistan: molecular analysis and identification of novel mutations
topic Short Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737203/
https://www.ncbi.nlm.nih.gov/pubmed/26096001
http://dx.doi.org/10.1111/cge.12622
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