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Case Report: Identification of a de novo Missense Mutation in the F8 Gene, p.(Phe690Leu)/c.2070C > A, Causing Hemophilia A: A Case Report
- Source :
- Frontiers in Genetics, Frontiers in Genetics, Vol 11 (2021)
- Publication Year :
- 2021
- Publisher :
- Frontiers Media SA, 2021.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
lcsh:QH426-470
Case Report
Single-nucleotide polymorphism
030204 cardiovascular system & hematology
Biology
03 medical and health sciences
symbols.namesake
0302 clinical medicine
chromosome copy number variation
single nucleotide polymorphism
Genetic linkage
hemic and lymphatic diseases
Genotype
medicine
Genetics
Missense mutation
p.(Phe690Leu)/c.2070C > A
Copy-number variation
Genetics (clinical)
Genetic testing
Sanger sequencing
medicine.diagnostic_test
lcsh:Genetics
030104 developmental biology
Mutation (genetic algorithm)
symbols
Molecular Medicine
hemophilia A
next-generation sequencing
preimplantation genetic testing for monogenic disease
Subjects
Details
- Language :
- English
- ISSN :
- 16648021
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Frontiers in Genetics
- Accession number :
- edsair.doi.dedup.....482c089484835906820b18d239cd187b
- Full Text :
- https://doi.org/10.3389/fgene.2020.589899