Novel PATL2 variants cause female infertility with oocyte maturation defect.

Autor: Hu HY; Birth Defects Prevention and Control Technology Research Center, Medical Innovation Research Division of Chinese, PLA General Hospital, Beijing, 100853, China., Zhang GH; Translational Medicine Research Center, Medical Innovation Research Division of Chinese, PLA General Hospital, Beijing, China., Deng WF; Shenzhen Hengsheng Hospital, Shenzhen, Guangdong, China., Wei TY; Jiaen Genetics Laboratory, Beijing Jiaen Hospital, Beijing, 100191, China., Feng ZK; Jiaen Genetics Laboratory, Beijing Jiaen Hospital, Beijing, 100191, China., Li CX; Jiaen Genetics Laboratory, Beijing Jiaen Hospital, Beijing, 100191, China., Li SJ; The Reproduction Medical Center, The Third Affiliated Hospital of Shenzhen University, Shenzhen, 518001, Guangdong, China. 13723470237@163.com., Liu JE; Jiaen Genetics Laboratory, Beijing Jiaen Hospital, Beijing, 100191, China. jiaenliu@jiaenhospital.com., Tian YP; Birth Defects Prevention and Control Technology Research Center, Medical Innovation Research Division of Chinese, PLA General Hospital, Beijing, 100853, China. tianyp@301hospital.com.cn.
Jazyk: angličtina
Zdroj: Journal of assisted reproduction and genetics [J Assist Reprod Genet] 2024 Aug; Vol. 41 (8), pp. 1965-1976. Date of Electronic Publication: 2024 Jul 02.
DOI: 10.1007/s10815-024-03150-5
Abstrakt: Purpose: Oocyte maturation defect (OOMD) is a rare cause of in vitro fertilization failure characterized by the production of immature oocytes. Compound heterozygous or homozygous PATL2 mutations have been associated with oocyte arrest at the germinal vesicle (GV), metaphase I (MI), and metaphase II (MII) stages, as well as morphological changes.
Methods: In this study, we recruited three OOMD cases and conducted a comprehensive multiplatform laboratory investigation.
Results: Whole exome sequence (WES) revealed four diagnostic variants in PATL2, nonsense mutation c.709C > T (p.R237*) and frameshift mutation c.1486_1487delinsT (p.A496Sfs*4) were novel mutations that have not been reported previously. Furthermore, the pathogenicity of these variants was predicted using in silico analysis, which indicated detrimental effects. Molecular dynamic analysis suggested that the A496S variant disrupted the hydrophobic segment, leading to structural changes that affected the overall protein folding and stability. Additionally, biochemical and molecular experiments were conducted on cells transfected with wild-type (WT) or mutant PATL2 (p.R237* and p.A496Sfs*4) plasmid vectors.
Conclusions: The results demonstrated that PATL2 A496Sfs*4 and PATL2 R237* had impacts on protein size and expression level. Interestingly, expression levels of specific genes involved in oocyte maturation and early embryonic development were found to be simultaneously deregulated. The findings in our study expand the variation spectrum of the PATL2 gene, provide solid evidence for counseling on future pregnancies in affected families, strongly support the application of in the diagnosis of OOMD, and contribute to the understanding of PATL2 function.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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