Analysis of a case with oocyte maturation disorder caused by a heterozygous c.728C>T (p.P243L) missense variant of TUBB8 gene and literature review.
10.3760/cma.j.cn511374-20241023-00553
- Author:
Wei JIANG
1
;
Yali NI
;
Jinwei YANG
;
Bo YAN
;
Chuan ZHANG
;
Zhiqiang WANG
Author Information
1. Center for Reproductive Medicine, Gansu Provincial Maternal and Child Health Care Hospital (Gansu Provincial Central Hospital), Gansu 730050, China. 303015412@qq.com.
- Publication Type:English Abstract
- MeSH:
Humans;
Female;
Adult;
Mutation, Missense;
Oocytes/metabolism*;
Heterozygote;
Tubulin/genetics*;
Infertility, Female/genetics*;
High-Throughput Nucleotide Sequencing;
Pedigree
- From:
Chinese Journal of Medical Genetics
2025;42(8):924-930
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the genetic basis for a woman with oocyte maturation disorder during assisted reproductive treatment (ART), and to verify the source of the variant and its impact on oocyte maturation through family verification.
METHODS:A 35-year-old infertile woman presented at the Reproductive Medicine Center of Gansu Provincial Maternal and Child Health Care Hospital on 20 October 2023 for a 10-year history of infertility despite unprotected intercourse was selected as study subject. Peripheral venous blood sample was collected from the proband. Next-generation sequencing (NGS) was used to detect the potential variant. Candidate variants were validated within her family by Sanger sequencing, and their deleteriousness was assessed with comprehensive bioinformatic analyses to elucidate their origin and impact on oocyte maturation. According to the Standards and Guidelines for the Interpretation of Sequence Variants (hereinafter referred to as ACMG Guidelines) formulated by the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Gansu Provincial Maternal and Child Health Care Hospital (Ethics No.: 2023GSFYLS78).
RESULTS:The proband underwent three controlled ovarian-stimulation cycles as part of assisted reproductive technology, yielding a total of 29 oocytes, among which only three were mature, whilst the remainders exhibited maturation arrest. Targeted sequencing of peripheral-blood DNA revealed a heterozygous c.728C>T (p.P243L) missense variant of the TUBB8 gene. While the same variant was detected in the proband's father. Based on the ACMG guidelines, the variant was classified to be likely pathogenic (PS4_Supporting+PM2_Supporting+PP2+PP3+PP4).
CONCLUSION:The heterozygous c.728C>T (p.P243L) missense variant of the TUBB8 gene probably underlay the oocyte maturation disorder in the proband, which may be either autosomal dominant or autosomal recessive. For probands with oocyte maturation disorders caused by the heterozygous c.728C>T variant of the TUBB8 gene, oocyte donation may be considered.
