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Integrative preimplantation genetic testing analysis for a Chinese family with hereditary spherocytosis caused by a novel splicing variant of SPTB

Hereditary spherocytosis (HS), the most common inherited hemolytic anemia disorder, is characterized by osmotically fragile microspherocytic red cells with a reduced surface area on the peripheral blood smear. Pathogenic variants in five erythrocyte membrane structure-related genes ANK1 (Spherocytos...

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Autores principales: Tian, Yafei, Wang, Yao, Yang, Jingmin, Gao, Pengfei, Xu, Hui, Wu, Yiming, Li, Mengru, Chen, Hongyan, Lu, Daru, Yan, Hongli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10545875/
https://www.ncbi.nlm.nih.gov/pubmed/37795245
http://dx.doi.org/10.3389/fgene.2023.1221853
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author Tian, Yafei
Wang, Yao
Yang, Jingmin
Gao, Pengfei
Xu, Hui
Wu, Yiming
Li, Mengru
Chen, Hongyan
Lu, Daru
Yan, Hongli
author_facet Tian, Yafei
Wang, Yao
Yang, Jingmin
Gao, Pengfei
Xu, Hui
Wu, Yiming
Li, Mengru
Chen, Hongyan
Lu, Daru
Yan, Hongli
author_sort Tian, Yafei
collection PubMed
description Hereditary spherocytosis (HS), the most common inherited hemolytic anemia disorder, is characterized by osmotically fragile microspherocytic red cells with a reduced surface area on the peripheral blood smear. Pathogenic variants in five erythrocyte membrane structure-related genes ANK1 (Spherocytosis, type 1; MIM#182900), SPTB (Spherocytosis, type 2; MIM#616649), SPTA1 (Spherocytosis, type 3; MIM#270970), SLC4A1 (Spherocytosis, type 4; MIM#612653) and EPB42 (Spherocytosis, type 5; MIM#612690) have been confirmed to be related to HS. There have been many studies on the pathogenic variants and mechanisms of HS, however, studies on how to manage the transmission of HS to the next-generation have not been reported. In this study, we recruited a patient with HS. Targeted next-generation sequencing with a panel of 208 genes related to blood system diseases detected a novel heterozygous variant in the SPTB: c.300+2dup in the proband. Sanger sequencing of variant alleles and haplotype linkage analysis of single nucleotide polymorphism (SNP) based on next-generation sequencing were performed simultaneously. Five embryos were identified with one heterozygous and four not carrying the SPTB variant. Single-cell amplification and whole genome sequencing showed that three embryos had varying degrees of trisomy mosaicism. One of two normal embryos was transferred to the proband. Ultimately, a healthy boy was born, confirmed by noninvasive prenatal testing for monogenic conditions (NIPT-M) to be disease-free. This confirmed our successful application of PGT in preventing transmission of the pathogenic variant allele in the HS family.
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spelling pubmed-105458752023-10-04 Integrative preimplantation genetic testing analysis for a Chinese family with hereditary spherocytosis caused by a novel splicing variant of SPTB Tian, Yafei Wang, Yao Yang, Jingmin Gao, Pengfei Xu, Hui Wu, Yiming Li, Mengru Chen, Hongyan Lu, Daru Yan, Hongli Front Genet Genetics Hereditary spherocytosis (HS), the most common inherited hemolytic anemia disorder, is characterized by osmotically fragile microspherocytic red cells with a reduced surface area on the peripheral blood smear. Pathogenic variants in five erythrocyte membrane structure-related genes ANK1 (Spherocytosis, type 1; MIM#182900), SPTB (Spherocytosis, type 2; MIM#616649), SPTA1 (Spherocytosis, type 3; MIM#270970), SLC4A1 (Spherocytosis, type 4; MIM#612653) and EPB42 (Spherocytosis, type 5; MIM#612690) have been confirmed to be related to HS. There have been many studies on the pathogenic variants and mechanisms of HS, however, studies on how to manage the transmission of HS to the next-generation have not been reported. In this study, we recruited a patient with HS. Targeted next-generation sequencing with a panel of 208 genes related to blood system diseases detected a novel heterozygous variant in the SPTB: c.300+2dup in the proband. Sanger sequencing of variant alleles and haplotype linkage analysis of single nucleotide polymorphism (SNP) based on next-generation sequencing were performed simultaneously. Five embryos were identified with one heterozygous and four not carrying the SPTB variant. Single-cell amplification and whole genome sequencing showed that three embryos had varying degrees of trisomy mosaicism. One of two normal embryos was transferred to the proband. Ultimately, a healthy boy was born, confirmed by noninvasive prenatal testing for monogenic conditions (NIPT-M) to be disease-free. This confirmed our successful application of PGT in preventing transmission of the pathogenic variant allele in the HS family. Frontiers Media S.A. 2023-09-18 /pmc/articles/PMC10545875/ /pubmed/37795245 http://dx.doi.org/10.3389/fgene.2023.1221853 Text en Copyright © 2023 Tian, Wang, Yang, Gao, Xu, Wu, Li, Chen, Lu and Yan. 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
Tian, Yafei
Wang, Yao
Yang, Jingmin
Gao, Pengfei
Xu, Hui
Wu, Yiming
Li, Mengru
Chen, Hongyan
Lu, Daru
Yan, Hongli
Integrative preimplantation genetic testing analysis for a Chinese family with hereditary spherocytosis caused by a novel splicing variant of SPTB
title Integrative preimplantation genetic testing analysis for a Chinese family with hereditary spherocytosis caused by a novel splicing variant of SPTB
title_full Integrative preimplantation genetic testing analysis for a Chinese family with hereditary spherocytosis caused by a novel splicing variant of SPTB
title_fullStr Integrative preimplantation genetic testing analysis for a Chinese family with hereditary spherocytosis caused by a novel splicing variant of SPTB
title_full_unstemmed Integrative preimplantation genetic testing analysis for a Chinese family with hereditary spherocytosis caused by a novel splicing variant of SPTB
title_short Integrative preimplantation genetic testing analysis for a Chinese family with hereditary spherocytosis caused by a novel splicing variant of SPTB
title_sort integrative preimplantation genetic testing analysis for a chinese family with hereditary spherocytosis caused by a novel splicing variant of sptb
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10545875/
https://www.ncbi.nlm.nih.gov/pubmed/37795245
http://dx.doi.org/10.3389/fgene.2023.1221853
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