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Case report: Preimplantation genetic testing for X-linked alport syndrome caused by variation in the COL4A5 gene

X-Linked Alport Syndrome (XLAS) is an X-linked, dominant, hereditary nephropathy mainly caused by mutations in the COL4A5 gene, found on chromosome Xq22. In this study, we reported a pedigree with XLAS caused by a COL4A5 mutation. This family gave birth to a boy with XLAS who developed hematuria and...

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Autores principales: Liu, Nengqing, Wen, Xiaojun, Ou, Zhanhui, Fang, Xiaowu, Du, Jing, Lin, Xiufeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448762/
https://www.ncbi.nlm.nih.gov/pubmed/37635800
http://dx.doi.org/10.3389/fped.2023.1177019
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author Liu, Nengqing
Wen, Xiaojun
Ou, Zhanhui
Fang, Xiaowu
Du, Jing
Lin, Xiufeng
author_facet Liu, Nengqing
Wen, Xiaojun
Ou, Zhanhui
Fang, Xiaowu
Du, Jing
Lin, Xiufeng
author_sort Liu, Nengqing
collection PubMed
description X-Linked Alport Syndrome (XLAS) is an X-linked, dominant, hereditary nephropathy mainly caused by mutations in the COL4A5 gene, found on chromosome Xq22. In this study, we reported a pedigree with XLAS caused by a COL4A5 mutation. This family gave birth to a boy with XLAS who developed hematuria and proteinuria at the age of 1 year. We used next-generation sequencing (NGS) to identify mutations in the proband and his parents and confirmed the results using Sanger sequencing. This testing showed there was a single nucleotide missense variation, c.3659G>A (p.Gly1220Asp) (NM_033380.3), in the COL4A5 gene. To prevent the inheritance of the syndrome, we used eight embryos for trophoblast biopsy after assisted reproductive technology treatment, and whole genome amplification (WGA) was performed using multiple annealing and looping-based amplification cycles (MALBAC). Embryos were subjected to Preimplantation Genetic Testing (PGT) procedures, including Sanger sequencing, NGS-based single nucleotide polymorphism (SNP) haplotype linkage analysis, and chromosomal copy number variation (CNV) analysis. The results showed that three embryos (E1, E2, and E4) were free of CNV and genetic variation in the COL4A5 gene. Embryo E1 (4AA) was transferred after consideration of the embryo growth rate, morphology, and PGT results. Prenatal diagnosis in the second trimester showed that the fetus had a normal karyotype and did not carry the COL4A5 mutation (c.3659G>A). Ultimately, a healthy boy was born and did not carry the pathogenic COL4A5 mutation, which indicated that PGT prevented the intergenerational transmission of the causative mutation of XLAS.
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spelling pubmed-104487622023-08-25 Case report: Preimplantation genetic testing for X-linked alport syndrome caused by variation in the COL4A5 gene Liu, Nengqing Wen, Xiaojun Ou, Zhanhui Fang, Xiaowu Du, Jing Lin, Xiufeng Front Pediatr Pediatrics X-Linked Alport Syndrome (XLAS) is an X-linked, dominant, hereditary nephropathy mainly caused by mutations in the COL4A5 gene, found on chromosome Xq22. In this study, we reported a pedigree with XLAS caused by a COL4A5 mutation. This family gave birth to a boy with XLAS who developed hematuria and proteinuria at the age of 1 year. We used next-generation sequencing (NGS) to identify mutations in the proband and his parents and confirmed the results using Sanger sequencing. This testing showed there was a single nucleotide missense variation, c.3659G>A (p.Gly1220Asp) (NM_033380.3), in the COL4A5 gene. To prevent the inheritance of the syndrome, we used eight embryos for trophoblast biopsy after assisted reproductive technology treatment, and whole genome amplification (WGA) was performed using multiple annealing and looping-based amplification cycles (MALBAC). Embryos were subjected to Preimplantation Genetic Testing (PGT) procedures, including Sanger sequencing, NGS-based single nucleotide polymorphism (SNP) haplotype linkage analysis, and chromosomal copy number variation (CNV) analysis. The results showed that three embryos (E1, E2, and E4) were free of CNV and genetic variation in the COL4A5 gene. Embryo E1 (4AA) was transferred after consideration of the embryo growth rate, morphology, and PGT results. Prenatal diagnosis in the second trimester showed that the fetus had a normal karyotype and did not carry the COL4A5 mutation (c.3659G>A). Ultimately, a healthy boy was born and did not carry the pathogenic COL4A5 mutation, which indicated that PGT prevented the intergenerational transmission of the causative mutation of XLAS. Frontiers Media S.A. 2023-08-10 /pmc/articles/PMC10448762/ /pubmed/37635800 http://dx.doi.org/10.3389/fped.2023.1177019 Text en © 2023 Liu, Wen, Ou, Fang, Du and Lin. 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) (https://creativecommons.org/licenses/by/4.0/) . 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
Liu, Nengqing
Wen, Xiaojun
Ou, Zhanhui
Fang, Xiaowu
Du, Jing
Lin, Xiufeng
Case report: Preimplantation genetic testing for X-linked alport syndrome caused by variation in the COL4A5 gene
title Case report: Preimplantation genetic testing for X-linked alport syndrome caused by variation in the COL4A5 gene
title_full Case report: Preimplantation genetic testing for X-linked alport syndrome caused by variation in the COL4A5 gene
title_fullStr Case report: Preimplantation genetic testing for X-linked alport syndrome caused by variation in the COL4A5 gene
title_full_unstemmed Case report: Preimplantation genetic testing for X-linked alport syndrome caused by variation in the COL4A5 gene
title_short Case report: Preimplantation genetic testing for X-linked alport syndrome caused by variation in the COL4A5 gene
title_sort case report: preimplantation genetic testing for x-linked alport syndrome caused by variation in the col4a5 gene
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448762/
https://www.ncbi.nlm.nih.gov/pubmed/37635800
http://dx.doi.org/10.3389/fped.2023.1177019
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