Cargando…

Case Report: Identification of a de novo Missense Mutation in the F8 Gene, p.(Phe690Leu)/c.2070C > A, Causing Hemophilia A: A Case Report

Hemophilia A is an X-linked recessive bleeding disorder caused by various types of pathological defects in the factor VIII gene (F8/FVIII). Preimplantation genetic testing for monogenic disease (PGT-M) is a powerful tool to tackle the transmission of monogenic inherited disorders from generation to...

Descripción completa

Detalles Bibliográficos
Autores principales: Bai, Haiyan, Xue, Xia, Tian, Li, Liu, Xi Tong, Li, Qian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973284/
https://www.ncbi.nlm.nih.gov/pubmed/33747028
http://dx.doi.org/10.3389/fgene.2020.589899
_version_ 1783666816518717440
author Bai, Haiyan
Xue, Xia
Tian, Li
Liu, Xi Tong
Li, Qian
author_facet Bai, Haiyan
Xue, Xia
Tian, Li
Liu, Xi Tong
Li, Qian
author_sort Bai, Haiyan
collection PubMed
description Hemophilia A is an X-linked recessive bleeding disorder caused by various types of pathological defects in the factor VIII gene (F8/FVIII). Preimplantation genetic testing for monogenic disease (PGT-M) is a powerful tool to tackle the transmission of monogenic inherited disorders from generation to generation. In our case, a mutation in F8 had passed through female carriers in a hemophilia A family and resulted in two male patients with hemophilia A. To identify the etiological genetic variants of F8, next-generation sequencing (NGS) was used for chromosome copy number variation detection, Sanger sequencing to verify mutation sites, single nucleotide polymorphism (SNP) for site amplification, and sequencing to validate the genetic linkage. Finally, a novel missense mutation, p. (Phe690Leu)/c.2070C > A, occurring in exon 13 of F8, was screened out as a pathogenic mutation. Following this, an F8 normal euploid blastocyst was transferred. At the 18th week, the pregnant mother underwent amniocentesis, NGS, Sanger sequencing, and SNP typing that further confirmed that the fetus had a healthy genotype. After delivery, a neonatal blood sample was sent for FVIII concentration detection, and the result established that the FVIII protein was rescued to a nearly average level. We first identified a new type of pathogenic mutation in F8, which has not been previously reported, selected a genetically healthy progeny for an affected family, and provided valuable knowledge of the diagnosis and treatment of hemophilia A.
format Online
Article
Text
id pubmed-7973284
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-79732842021-03-20 Case Report: Identification of a de novo Missense Mutation in the F8 Gene, p.(Phe690Leu)/c.2070C > A, Causing Hemophilia A: A Case Report Bai, Haiyan Xue, Xia Tian, Li Liu, Xi Tong Li, Qian Front Genet Genetics Hemophilia A is an X-linked recessive bleeding disorder caused by various types of pathological defects in the factor VIII gene (F8/FVIII). Preimplantation genetic testing for monogenic disease (PGT-M) is a powerful tool to tackle the transmission of monogenic inherited disorders from generation to generation. In our case, a mutation in F8 had passed through female carriers in a hemophilia A family and resulted in two male patients with hemophilia A. To identify the etiological genetic variants of F8, next-generation sequencing (NGS) was used for chromosome copy number variation detection, Sanger sequencing to verify mutation sites, single nucleotide polymorphism (SNP) for site amplification, and sequencing to validate the genetic linkage. Finally, a novel missense mutation, p. (Phe690Leu)/c.2070C > A, occurring in exon 13 of F8, was screened out as a pathogenic mutation. Following this, an F8 normal euploid blastocyst was transferred. At the 18th week, the pregnant mother underwent amniocentesis, NGS, Sanger sequencing, and SNP typing that further confirmed that the fetus had a healthy genotype. After delivery, a neonatal blood sample was sent for FVIII concentration detection, and the result established that the FVIII protein was rescued to a nearly average level. We first identified a new type of pathogenic mutation in F8, which has not been previously reported, selected a genetically healthy progeny for an affected family, and provided valuable knowledge of the diagnosis and treatment of hemophilia A. Frontiers Media S.A. 2021-03-05 /pmc/articles/PMC7973284/ /pubmed/33747028 http://dx.doi.org/10.3389/fgene.2020.589899 Text en Copyright © 2021 Bai, Xue, Tian, Liu and Li. http://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 Genetics
Bai, Haiyan
Xue, Xia
Tian, Li
Liu, Xi Tong
Li, Qian
Case Report: Identification of a de novo Missense Mutation in the F8 Gene, p.(Phe690Leu)/c.2070C > A, Causing Hemophilia A: A Case Report
title Case Report: Identification of a de novo Missense Mutation in the F8 Gene, p.(Phe690Leu)/c.2070C > A, Causing Hemophilia A: A Case Report
title_full Case Report: Identification of a de novo Missense Mutation in the F8 Gene, p.(Phe690Leu)/c.2070C > A, Causing Hemophilia A: A Case Report
title_fullStr Case Report: Identification of a de novo Missense Mutation in the F8 Gene, p.(Phe690Leu)/c.2070C > A, Causing Hemophilia A: A Case Report
title_full_unstemmed Case Report: Identification of a de novo Missense Mutation in the F8 Gene, p.(Phe690Leu)/c.2070C > A, Causing Hemophilia A: A Case Report
title_short Case Report: Identification of a de novo Missense Mutation in the F8 Gene, p.(Phe690Leu)/c.2070C > A, Causing Hemophilia A: A Case Report
title_sort case report: identification of a de novo missense mutation in the f8 gene, p.(phe690leu)/c.2070c > a, causing hemophilia a: a case report
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973284/
https://www.ncbi.nlm.nih.gov/pubmed/33747028
http://dx.doi.org/10.3389/fgene.2020.589899
work_keys_str_mv AT baihaiyan casereportidentificationofadenovomissensemutationinthef8genepphe690leuc2070cacausinghemophiliaaacasereport
AT xuexia casereportidentificationofadenovomissensemutationinthef8genepphe690leuc2070cacausinghemophiliaaacasereport
AT tianli casereportidentificationofadenovomissensemutationinthef8genepphe690leuc2070cacausinghemophiliaaacasereport
AT liuxitong casereportidentificationofadenovomissensemutationinthef8genepphe690leuc2070cacausinghemophiliaaacasereport
AT liqian casereportidentificationofadenovomissensemutationinthef8genepphe690leuc2070cacausinghemophiliaaacasereport