Whole exome sequencing for diagnosis of hereditary thrombocytopenia
Autor: | Ponthip Mekchay, Suwanna Muanpetch, Supang Maneesri le Grand, Chupong Ittiwut, Weerapan Khovidhunkit, Darintr Sosothikul, Benjaporn Akkawat, Rungnapa Ittiwut, Netchanok Leela-Adisorn, Ponlapat Rojnuckarin, Kanya Suphapeetiporn, Vorasuk Shotelersuk |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Adult
Pathology medicine.medical_specialty Adolescent Observational Study Compound heterozygosity medicine.disease_cause Bernard–Soulier syndrome whole exome sequencing 03 medical and health sciences chemistry.chemical_compound Young Adult 0302 clinical medicine Exome Sequencing Medicine Humans 030212 general & internal medicine Allele Ristocetin Exome sequencing Mutation business.industry General Medicine Middle Aged medicine.disease Thrombocytopenia GP1BA hereditary platelet disorders Cross-Sectional Studies chemistry 030220 oncology & carcinogenesis platelets Female business Sitosterolemia Research Article |
Zdroj: | Medicine |
ISSN: | 1536-5964 0025-7974 |
Popis: | 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. |
Databáze: | OpenAIRE |
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