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F8 gene inversion and duplication cause no obvious hemophilia A phenotype

Hemophilia A (HA, OMIM#306700) is an X-linked recessive bleeding disorder caused by the defects in the F8 gene, which encodes coagulation factor VIII (FVIII). Intron 22 inversion (Inv22) is found in about 45% of patients with severe hemophilia A. Here, we reported a male without obvious hemophilia A...

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Autores principales: Li, Shaoying, He, Jianchun, Chu, Liming, Ren, Shuai, He, Wenzhi, Ma, Xiaoyan, Wang, Yanchao, Zhang, Mincong, Kong, Lingyin, Liang, Bo, Li, Qing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9947239/
https://www.ncbi.nlm.nih.gov/pubmed/36845383
http://dx.doi.org/10.3389/fgene.2023.1098795
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author Li, Shaoying
He, Jianchun
Chu, Liming
Ren, Shuai
He, Wenzhi
Ma, Xiaoyan
Wang, Yanchao
Zhang, Mincong
Kong, Lingyin
Liang, Bo
Li, Qing
author_facet Li, Shaoying
He, Jianchun
Chu, Liming
Ren, Shuai
He, Wenzhi
Ma, Xiaoyan
Wang, Yanchao
Zhang, Mincong
Kong, Lingyin
Liang, Bo
Li, Qing
author_sort Li, Shaoying
collection PubMed
description Hemophilia A (HA, OMIM#306700) is an X-linked recessive bleeding disorder caused by the defects in the F8 gene, which encodes coagulation factor VIII (FVIII). Intron 22 inversion (Inv22) is found in about 45% of patients with severe hemophilia A. Here, we reported a male without obvious hemophilia A phenotype but bearing an inherited segmental variant duplication encompassing F8 as well as Inv22. The duplication was approximately 0.16 Mb and involved from exon 1 to intron 22 of F8. This partial duplication and Inv22 in F8 was first found in the abortion tissue of his older sister with recurrent miscarriage. The genetic testing of his family revealed that his phenotypically normal older sister and mother also had this heterozygous Inv22 and a 0.16 Mb partial duplication of F8, while his father was genotypically normal. The integrity of the F8 gene transcript was verified by sequencing of the adjacent exons at the inversion breakpoint, which explained why this male had no phenotype for hemophilia A. Interestingly, although he had no significant hemophilia A phenotype, the expression of C1QA in his mother, sister, and the male subject was only about half of that in his father and normal population. Our report broadens the mutation spectrum of F8 inversion and duplication and its pathogenicity in hemophilia A.
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spelling pubmed-99472392023-02-24 F8 gene inversion and duplication cause no obvious hemophilia A phenotype Li, Shaoying He, Jianchun Chu, Liming Ren, Shuai He, Wenzhi Ma, Xiaoyan Wang, Yanchao Zhang, Mincong Kong, Lingyin Liang, Bo Li, Qing Front Genet Genetics Hemophilia A (HA, OMIM#306700) is an X-linked recessive bleeding disorder caused by the defects in the F8 gene, which encodes coagulation factor VIII (FVIII). Intron 22 inversion (Inv22) is found in about 45% of patients with severe hemophilia A. Here, we reported a male without obvious hemophilia A phenotype but bearing an inherited segmental variant duplication encompassing F8 as well as Inv22. The duplication was approximately 0.16 Mb and involved from exon 1 to intron 22 of F8. This partial duplication and Inv22 in F8 was first found in the abortion tissue of his older sister with recurrent miscarriage. The genetic testing of his family revealed that his phenotypically normal older sister and mother also had this heterozygous Inv22 and a 0.16 Mb partial duplication of F8, while his father was genotypically normal. The integrity of the F8 gene transcript was verified by sequencing of the adjacent exons at the inversion breakpoint, which explained why this male had no phenotype for hemophilia A. Interestingly, although he had no significant hemophilia A phenotype, the expression of C1QA in his mother, sister, and the male subject was only about half of that in his father and normal population. Our report broadens the mutation spectrum of F8 inversion and duplication and its pathogenicity in hemophilia A. Frontiers Media S.A. 2023-02-09 /pmc/articles/PMC9947239/ /pubmed/36845383 http://dx.doi.org/10.3389/fgene.2023.1098795 Text en Copyright © 2023 Li, He, Chu, Ren, He, Ma, Wang, Zhang, Kong, Liang and Li. 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 Genetics
Li, Shaoying
He, Jianchun
Chu, Liming
Ren, Shuai
He, Wenzhi
Ma, Xiaoyan
Wang, Yanchao
Zhang, Mincong
Kong, Lingyin
Liang, Bo
Li, Qing
F8 gene inversion and duplication cause no obvious hemophilia A phenotype
title F8 gene inversion and duplication cause no obvious hemophilia A phenotype
title_full F8 gene inversion and duplication cause no obvious hemophilia A phenotype
title_fullStr F8 gene inversion and duplication cause no obvious hemophilia A phenotype
title_full_unstemmed F8 gene inversion and duplication cause no obvious hemophilia A phenotype
title_short F8 gene inversion and duplication cause no obvious hemophilia A phenotype
title_sort f8 gene inversion and duplication cause no obvious hemophilia a phenotype
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9947239/
https://www.ncbi.nlm.nih.gov/pubmed/36845383
http://dx.doi.org/10.3389/fgene.2023.1098795
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