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Case Report: Exome Sequencing Identified a Novel Frameshift Mutation of α-Actin 1 in a Chinese Family With Macrothrombocytopenia and Mild Bleeding

Inherited macrothrombocytopenia (IMTP) is a rare disorder characterized by a reduced platelet count and abnormally large platelets. The main clinical symptom of IMTP is mild bleeding in some patients. At present, more than 30 genes have been identified in patients with syndromic and non-syndromic IM...

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Autores principales: Luo, Fang-Mei, Fan, Liang-Liang, Sheng, Yue, Dong, Yi, Liu, Lv
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253534/
https://www.ncbi.nlm.nih.gov/pubmed/34222148
http://dx.doi.org/10.3389/fped.2021.679279
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author Luo, Fang-Mei
Fan, Liang-Liang
Sheng, Yue
Dong, Yi
Liu, Lv
author_facet Luo, Fang-Mei
Fan, Liang-Liang
Sheng, Yue
Dong, Yi
Liu, Lv
author_sort Luo, Fang-Mei
collection PubMed
description Inherited macrothrombocytopenia (IMTP) is a rare disorder characterized by a reduced platelet count and abnormally large platelets. The main clinical symptom of IMTP is mild bleeding in some patients. At present, more than 30 genes have been identified in patients with syndromic and non-syndromic IMTP. In this study, a 3-year-old boy and his mother who presented with mild epistaxis and/or gingival bleeding were diagnosed as having IMTP. Wen then selected whole sequencing to explore the genetic lesion of the patients. After data filtering and mutation validation, a novel frameshift mutation (NM_001130004: c.398_399insTGCG, p.F134AfsX60) of α-actin 1 (ACTN1) was identified in the proband and his mother but absent in other unaffected individuals. Previous studies have proven that mutations in ACTN1 may lead to IMTP with mild to absent bleeding phenotype. The novel mutation, resulting in a truncated protein in exon 4 of the ACTN1 gene, was absent in the public database, such as 1000G and genomAD. Further Western blot revealed that the expression of α-actin 1 in the proband was decreased overtly, which indicated that the novel frameshift mutation may induce non-sense-mediated mRNA decay. In summary, this study not only broadened the variants spectrum of ACTN1 gene, which may contribute to the genetic counseling of IMTP, but also confirmed the diagnosis of IMTP, which may help the management and prognosis for the family members.
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spelling pubmed-82535342021-07-03 Case Report: Exome Sequencing Identified a Novel Frameshift Mutation of α-Actin 1 in a Chinese Family With Macrothrombocytopenia and Mild Bleeding Luo, Fang-Mei Fan, Liang-Liang Sheng, Yue Dong, Yi Liu, Lv Front Pediatr Pediatrics Inherited macrothrombocytopenia (IMTP) is a rare disorder characterized by a reduced platelet count and abnormally large platelets. The main clinical symptom of IMTP is mild bleeding in some patients. At present, more than 30 genes have been identified in patients with syndromic and non-syndromic IMTP. In this study, a 3-year-old boy and his mother who presented with mild epistaxis and/or gingival bleeding were diagnosed as having IMTP. Wen then selected whole sequencing to explore the genetic lesion of the patients. After data filtering and mutation validation, a novel frameshift mutation (NM_001130004: c.398_399insTGCG, p.F134AfsX60) of α-actin 1 (ACTN1) was identified in the proband and his mother but absent in other unaffected individuals. Previous studies have proven that mutations in ACTN1 may lead to IMTP with mild to absent bleeding phenotype. The novel mutation, resulting in a truncated protein in exon 4 of the ACTN1 gene, was absent in the public database, such as 1000G and genomAD. Further Western blot revealed that the expression of α-actin 1 in the proband was decreased overtly, which indicated that the novel frameshift mutation may induce non-sense-mediated mRNA decay. In summary, this study not only broadened the variants spectrum of ACTN1 gene, which may contribute to the genetic counseling of IMTP, but also confirmed the diagnosis of IMTP, which may help the management and prognosis for the family members. Frontiers Media S.A. 2021-06-18 /pmc/articles/PMC8253534/ /pubmed/34222148 http://dx.doi.org/10.3389/fped.2021.679279 Text en Copyright © 2021 Luo, Fan, Sheng, Dong and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Luo, Fang-Mei
Fan, Liang-Liang
Sheng, Yue
Dong, Yi
Liu, Lv
Case Report: Exome Sequencing Identified a Novel Frameshift Mutation of α-Actin 1 in a Chinese Family With Macrothrombocytopenia and Mild Bleeding
title Case Report: Exome Sequencing Identified a Novel Frameshift Mutation of α-Actin 1 in a Chinese Family With Macrothrombocytopenia and Mild Bleeding
title_full Case Report: Exome Sequencing Identified a Novel Frameshift Mutation of α-Actin 1 in a Chinese Family With Macrothrombocytopenia and Mild Bleeding
title_fullStr Case Report: Exome Sequencing Identified a Novel Frameshift Mutation of α-Actin 1 in a Chinese Family With Macrothrombocytopenia and Mild Bleeding
title_full_unstemmed Case Report: Exome Sequencing Identified a Novel Frameshift Mutation of α-Actin 1 in a Chinese Family With Macrothrombocytopenia and Mild Bleeding
title_short Case Report: Exome Sequencing Identified a Novel Frameshift Mutation of α-Actin 1 in a Chinese Family With Macrothrombocytopenia and Mild Bleeding
title_sort case report: exome sequencing identified a novel frameshift mutation of α-actin 1 in a chinese family with macrothrombocytopenia and mild bleeding
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253534/
https://www.ncbi.nlm.nih.gov/pubmed/34222148
http://dx.doi.org/10.3389/fped.2021.679279
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