Preimplantation Genetic Testing Prevented Intergenerational Transmission of X-Linked Alport Syndrome-Reference-Cited by-同舟云学术

Preimplantation Genetic Testing Prevented Intergenerational Transmission of X-Linked Alport Syndrome

Published:2021 Issue:6 Volume:7 Page:514-520
ISSN:2296-9381
Container-title:Kidney Diseases
language:en
Short-container-title:Kidney Dis

Author:

Hu Xiaoling,Zhang Jiahui,Lv Yuan,Chen Xijing,Feng Guofang,Wang Liya,Ye Yinghui,Jin Fan,Zhu Yimin

Abstract

Background: Alport syndrome (AS) is a hereditary renal basement membrane disease that can lead to end-stage renal disease in young adults. It can be diagnosed by genetic analysis, being mostly caused by mutations in COL4A3, COL4A4, and COL4A5. To date, there is no radical cure for this disease. Objectives: The aim of this study was to avoid the transmission of AS within an affected family by selecting healthy embryos for uterine transfer. The embryos were identified by preimplantation genetic testing for monogenic disorders (PGT-M). Methods: We used next-generation sequencing (NGS) to identify mutations in the proband and his parents. The results of NGS were confirmed by Sanger sequencing. Targeted NGS combined with targeted single-nucleotide polymorphism haplotyping was used for the in vitro identification of COL4A5 mutations in human embryos to prevent their intergenerational transmission. Results: The c.349_359delGGACCTCAAGG and c.360_361insTGC mutations in COL4A5 were identified in a family affected by X-linked AS. Whole-genome sequencing by NGS with targeted haplotyping was performed on biopsied trophectoderm cells. A healthy baby was born after transfer of a single freeze-thawed blastocyst. Conclusions: The use of targeted NGS for identifying diagnostic markers combined with targeted haplotyping is an easy and efficient PGT-M method for preventing intergenerational transmission of AS.

Publisher

S. Karger AG

Subject

Materials Chemistry

Reference34 articles.

1. Gubler MC. Inherited diseases of the glomerular basement membrane. Nat Clin Pract Nephrol. 2008;4(1):24–37.

2. Savige J, Gregory M, Gross O, Kashtan C, Ding J, Flinter F. Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. J Am Soc Nephrol. 2013;24(3):364–75.

3. Zhao X, Chen C, Wei Y, Zhao G, Liu L, Wang C, et al. Novel mutations of COL4A3, COL4A4, and COL4A5 genes in Chinese patients with Alport Syndrome using next generation sequence technique. Mol Genet Genomic Med. 2019;7(6):e653.

4. Barker DF, Hostikka SL, Zhou J, Chow LT, Oliphant AR, Gerken SC, et al. Identification of mutations in the COL4A5 collagen gene in Alport syndrome. Science. 1990;248(4960):1224–7.

5. Heidet L, Arrondel C, Forestier L, Cohen-Solal L, Mollet G, Gutierrez B, et al. Structure of the human type IV collagen gene COL4A3 and mutations in autosomal Alport syndrome. J Am Soc Nephrol. 2001;12(1):97–106.

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1. Case report: Preimplantation genetic testing for X-linked alport syndrome caused by variation in the COL4A5 gene;Frontiers in Pediatrics;2023-08-10