Whole exome sequencing for diagnosis of hereditary thrombocytopenia
Hereditary thrombocytopenia comprises extremely diverse diseases that are difficult to diagnose by phenotypes alone. Definite diagnoses are helpful for patient (Pt) management. To evaluate the role of whole exome sequencing (WES) in these Pts. Cases with unexplained long-standing thrombocytopenia an...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676547/ https://www.ncbi.nlm.nih.gov/pubmed/33217855 http://dx.doi.org/10.1097/MD.0000000000023275 |
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author | Mekchay, Ponthip Ittiwut, Chupong Ittiwut, Rungnapa Akkawat, Benjaporn Le Grand, Supang Maneesri Leela-adisorn, Netchanok Muanpetch, Suwanna Khovidhunkit, Weerapan Sosothikul, Darintr Shotelersuk, Vorasuk Suphapeetiporn, Kanya Rojnuckarin, Ponlapat |
author_facet | Mekchay, Ponthip Ittiwut, Chupong Ittiwut, Rungnapa Akkawat, Benjaporn Le Grand, Supang Maneesri Leela-adisorn, Netchanok Muanpetch, Suwanna Khovidhunkit, Weerapan Sosothikul, Darintr Shotelersuk, Vorasuk Suphapeetiporn, Kanya Rojnuckarin, Ponlapat |
author_sort | Mekchay, Ponthip |
collection | PubMed |
description | Hereditary thrombocytopenia comprises extremely diverse diseases that are difficult to diagnose by phenotypes alone. Definite diagnoses are helpful for patient (Pt) management. To evaluate the role of whole exome sequencing (WES) in these Pts. Cases with unexplained long-standing thrombocytopenia and/or suggestive features were enrolled to the observational study. Bleeding scores and blood smear were evaluated. The variant pathogenicity from WES was determined by bioinformatics combined with all other information including platelet aggregometry, flow cytometry, and electron microscopy (EM). Seven unrelated Pts were recruited. All were female with macrothrombocytopenia. Clinical bleeding was presented in four Pts; extra-hematological features were minimal and family history was negative in every Pt. WES successfully identified all the 11 responsible mutant alleles; of these, four have never been previously reported. Pt 1 with GNE-related thrombocytopenia showed reduced lectin binding by flow cytometry, increased glycogen granules by EM and a novel homozygous mutation in GNE. Pts 2 and 3 had phenotypic diagnoses of Bernard Soulier syndrome and novel homozygous mutations in GP1BB and GP1BA, respectively. Pt 4 had impaired microtubule structures, concomitant delta storage pool disease by EM and a novel heterozygous TUBB1 mutation. Pt 5 had sitosterolemia showing platelets with reduced ristocetin responses and a dilated membrane system on EM with compound heterozygous ABCG5 mutations. Pts 6 and 7 had MYH9 disorders with heterozygous mutations in MYH9. This study substantiates the benefits of WES in identifying underlying mutations of macrothrombocytopenia, expands mutational spectra of four genes, and provides detailed clinical features for further phenotype-genotype correlations. |
format | Online Article Text |
id | pubmed-7676547 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-76765472020-11-24 Whole exome sequencing for diagnosis of hereditary thrombocytopenia Mekchay, Ponthip Ittiwut, Chupong Ittiwut, Rungnapa Akkawat, Benjaporn Le Grand, Supang Maneesri Leela-adisorn, Netchanok Muanpetch, Suwanna Khovidhunkit, Weerapan Sosothikul, Darintr Shotelersuk, Vorasuk Suphapeetiporn, Kanya Rojnuckarin, Ponlapat Medicine (Baltimore) 4800 Hereditary thrombocytopenia comprises extremely diverse diseases that are difficult to diagnose by phenotypes alone. Definite diagnoses are helpful for patient (Pt) management. To evaluate the role of whole exome sequencing (WES) in these Pts. Cases with unexplained long-standing thrombocytopenia and/or suggestive features were enrolled to the observational study. Bleeding scores and blood smear were evaluated. The variant pathogenicity from WES was determined by bioinformatics combined with all other information including platelet aggregometry, flow cytometry, and electron microscopy (EM). Seven unrelated Pts were recruited. All were female with macrothrombocytopenia. Clinical bleeding was presented in four Pts; extra-hematological features were minimal and family history was negative in every Pt. WES successfully identified all the 11 responsible mutant alleles; of these, four have never been previously reported. Pt 1 with GNE-related thrombocytopenia showed reduced lectin binding by flow cytometry, increased glycogen granules by EM and a novel homozygous mutation in GNE. Pts 2 and 3 had phenotypic diagnoses of Bernard Soulier syndrome and novel homozygous mutations in GP1BB and GP1BA, respectively. Pt 4 had impaired microtubule structures, concomitant delta storage pool disease by EM and a novel heterozygous TUBB1 mutation. Pt 5 had sitosterolemia showing platelets with reduced ristocetin responses and a dilated membrane system on EM with compound heterozygous ABCG5 mutations. Pts 6 and 7 had MYH9 disorders with heterozygous mutations in MYH9. This study substantiates the benefits of WES in identifying underlying mutations of macrothrombocytopenia, expands mutational spectra of four genes, and provides detailed clinical features for further phenotype-genotype correlations. Lippincott Williams & Wilkins 2020-11-20 /pmc/articles/PMC7676547/ /pubmed/33217855 http://dx.doi.org/10.1097/MD.0000000000023275 Text en Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc. http://creativecommons.org/licenses/by-nc/4.0 This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0 |
spellingShingle | 4800 Mekchay, Ponthip Ittiwut, Chupong Ittiwut, Rungnapa Akkawat, Benjaporn Le Grand, Supang Maneesri Leela-adisorn, Netchanok Muanpetch, Suwanna Khovidhunkit, Weerapan Sosothikul, Darintr Shotelersuk, Vorasuk Suphapeetiporn, Kanya Rojnuckarin, Ponlapat Whole exome sequencing for diagnosis of hereditary thrombocytopenia |
title | Whole exome sequencing for diagnosis of hereditary thrombocytopenia |
title_full | Whole exome sequencing for diagnosis of hereditary thrombocytopenia |
title_fullStr | Whole exome sequencing for diagnosis of hereditary thrombocytopenia |
title_full_unstemmed | Whole exome sequencing for diagnosis of hereditary thrombocytopenia |
title_short | Whole exome sequencing for diagnosis of hereditary thrombocytopenia |
title_sort | whole exome sequencing for diagnosis of hereditary thrombocytopenia |
topic | 4800 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676547/ https://www.ncbi.nlm.nih.gov/pubmed/33217855 http://dx.doi.org/10.1097/MD.0000000000023275 |
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