Biallelic Mutations in PATL2 Cause Female Infertility Characterized by Oocyte Maturation Arrest

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2017 Oct 3

PMID 28965849

Citations 69

Authors

Biaobang Chen

Zhihua Zhang

Xiaoxi Sun

Yanping Kuang

Xiaoyan Mao

Xueqian Wang

Zheng Yan

Bin Li

Yao Xu

Min Yu

Jing Fu

Jian Mu

Zhou Zhou

Qiaoli Li

Li Jin

Lin He

Qing Sang

Lei Wang

Affiliations

Soon will be listed here.

Abstract

Oocyte maturation arrest results in female infertility, but the genetic determinants of human oocyte maturation arrest remain largely unknown. Previously, we identified TUBB8 mutations responsible for human oocyte maturation arrest, indicating the important role of genetic factors in the disorder. However, TUBB8 mutations account for only around 30% of individuals with oocyte maturation arrest; thus, the disorder is likely to involve other genetic factors that are as yet unknown. Here, we initially identified a homozygous nonsense mutation of PATL2 (c.784C>T [p.Arg262]) in a consanguineous family with a phenotype characterized by human oocyte germinal vesicle (GV) arrest. Subsequent mutation screening of PATL2 in a cohort of 179 individuals identified four additional independent individuals with compound-heterozygous PATL2 mutations with slight phenotypic variability. A genetic burden test further confirmed the genetic contribution of PATL2 to human oocyte maturation arrest. By western blot in HeLa cells, identification of splicing events in affected individuals' granulosa cells, and immunostaining in affected individuals' oocytes, we provide evidence that mutations in PATL2 lead to decreased amounts of protein. These findings suggest an important role for PATL2 mutations in oocyte maturation arrest and expand our understanding of the genetic basis of female infertility.

Citing Articles

Evaluation of Risk Factors and a Gene Panel as a Tool for Unexplained Infertility Diagnosis by Next-Generation Sequencing.

Jasinskiene E, Snieckute I, Galminas I, Zemaitis L, Simutis M, caplinskiene M Medicina (Kaunas). 2025; 61(2).

PMID: 40005388 PMC: 11857236. DOI: 10.3390/medicina61020271.

Pathogenic variants of TUBB8 cause oocyte spindle defects by disrupting with EB1/CAKP5 interactions and potential treatment targeting microtubule acetylation through HDAC6 inhibition.

Luo H, Chen J, Li C, Wu T, Yin S, Yang G Clin Transl Med. 2025; 15(1):e70193.

PMID: 39834092 PMC: 11746963. DOI: 10.1002/ctm2.70193.

PATL2 mutations affect human oocyte maternal mRNA homeostasis and protein interactions in cell cycle regulation.

Zhang Y, Hu Z, Jiang H, Jin J, Zhou Y, Lai M Cell Biosci. 2024; 14(1):157.

PMID: 39741299 PMC: 11686847. DOI: 10.1186/s13578-024-01341-2.

Identification of a novel mutation in gene associated with the germinal vesicle arrest of oocytes.

Yu A, Huang Z, Shi H, Lin Y, Cai X, Ke Z Biochem Biophys Rep. 2024; 40:101886.

PMID: 39649799 PMC: 11625204. DOI: 10.1016/j.bbrep.2024.101886.

Novel splicing mutations in PATL2 and WEE2 cause oocyte degradation and fertilization failure.

Liu Z, Zhu L, He H, Hou M, Jia W, Jin L J Assist Reprod Genet. 2024; 41(12):3337-3345.

PMID: 39476306 PMC: 11707231. DOI: 10.1007/s10815-024-03260-0.

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