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

被引:127
作者
Chen, Biaobang [1 ,2 ]
Zhang, Zhihua [1 ]
Sun, Xiaoxi [3 ]
Kuang, Yanping [4 ]
Mao, Xiaoyan [4 ]
Wang, Xueqian [1 ]
Yan, Zheng [4 ]
Li, Bin [4 ]
Xu, Yao [1 ]
Yu, Min [3 ]
Fu, Jing [3 ]
Mu, Jian [1 ]
Zhou, Zhou [1 ]
Li, Qiaoli [1 ]
Jin, Li [1 ]
He, Lin [5 ,6 ]
Sang, Qing [1 ,2 ]
Wang, Lei [1 ,2 ]
机构
[1] Fudan Univ, State Key Lab Genet Engn, Zhongshan Hosp, Inst Biomed Sci,Sch Life Sci, Shanghai 200032, Peoples R China
[2] Guangzhou Med Univ, Guangzhou Med Univ & Guangzhou Inst Biomed & Hlth, Guangzhou 511436, Guangdong, Peoples R China
[3] Fudan Univ, Shanghai Ji Ai Genet & IVF Inst, Obstet & Gynecol Hosp, Shanghai 200011, Peoples R China
[4] Shanghai Jiao Tong Univ, Shanghai Hosp 9, Reprod Med Ctr, Shanghai 200011, Peoples R China
[5] Shanghai Jiao Tong Univ, Key Lab Genet Dev & Neuropsychiat Disorders, BioX Ctr, Minist Educ, Shanghai 200030, Peoples R China
[6] Guangzhou Med Univ, Affiliated Hosp 3, Lin Hes Acad Workstn New Med & Clin Translat, Guangzhou 510150, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
SEQUENCING DATA; MEIOTIC ARREST; TUBB8; FERTILIZATION; NUCLEAR; XENOPUS; WOMEN;
D O I
10.1016/j.ajhg.2017.08.018
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:609 / 615
页数:7
相关论文
共 21 条
  • [1] TLE6 mutation causes the earliest known human embryonic lethality
    Alazami, Anas M.
    Awad, Salma M.
    Coskun, Serdar
    Al-Hassan, Saad
    Hijazi, Hadia
    Abdulwahab, Firdous M.
    Poizat, Coralie
    Alkuraya, Fowzan S.
    [J]. GENOME BIOLOGY, 2015, 16
  • [2] An idiopathic infertility with oocytes metaphase I maturation block
    Bergère, M
    Lombroso, R
    Gombault, M
    Wainer, R
    Selva, J
    [J]. HUMAN REPRODUCTION, 2001, 16 (10) : 2136 - 2138
  • [3] Novel mutations and structural deletions in TUBB8: expanding mutational and phenotypic spectrum of patients with arrest in oocyte maturation, fertilization or early embryonic development
    Chen, Biaobang
    Li, Bin
    Li, Da
    Yan, Zheng
    Mao, Xiaoyan
    Xu, Yao
    Mu, Jian
    Li, Qiaoli
    Jin, Li
    He, Lin
    Kuang, Yanping
    Sang, Qing
    Wang, Lei
    [J]. HUMAN REPRODUCTION, 2017, 32 (02) : 457 - 464
  • [4] Exacting Requirements for Development of the Egg
    Dean, Jurrien
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2016, 374 (03) : 279 - 280
  • [5] EICHENLAUBRITTER U, 1995, HUM REPROD, V10, P2343
  • [7] Mutations in TUBB8 cause a multiplicity of phenotypes in human oocytes and early embryos
    Feng, Ruizhi
    Yan, Zheng
    Li, Bin
    Yu, Min
    Sang, Qing
    Tian, Guoling
    Xu, Yao
    Chen, Biaobang
    Qu, Ronggui
    Sun, Zhaogui
    Sun, Xiaoxi
    Jin, Li
    He, Lin
    Kuang, Yanping
    Cowan, Nicholas J.
    Wang, Lei
    [J]. JOURNAL OF MEDICAL GENETICS, 2016, 53 (10) : 662 - 671
  • [8] Mutations in TUBB8 and Human Oocyte Meiotic Arrest
    Feng, Ruizhi
    Sang, Qing
    Kuang, Yanping
    Sun, Xiaoxi
    Yan, Zheng
    Zhang, Shaozhen
    Shi, Juanzi
    Tian, Guoling
    Luchniak, Anna
    Fukuda, Yusuke
    Li, Bin
    Yu, Min
    Chen, Junling
    Xu, Yao
    Guo, Luo
    Qu, Ronggui
    Wang, Xueqian
    Sun, Zhaogui
    Liu, Miao
    Shi, Huijuan
    Wang, Hongyan
    Feng, Yi
    Shao, Ruijin
    Chai, Renjie
    Li, Qiaoli
    Xing, Qinghe
    Zhang, Rui
    Nogales, Eva
    Jin, Li
    He, Lin
    Gupta, Mohan L., Jr.
    Cowan, Nicholas J.
    Wang, Lei
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2016, 374 (03) : 223 - 232
  • [9] A case of failed oocyte maturation in vivo and in vitro
    Hartshorne, G
    Montgomery, S
    Klentzeris, L
    [J]. FERTILITY AND STERILITY, 1999, 71 (03) : 567 - 570
  • [10] Mutation analysis of the TUBB8 gene in nine infertile women with oocyte maturation arrest
    Huang, Lingli
    Tong, Xianhong
    Luo, Lihua
    Zheng, Shengxia
    Jin, Rentao
    Fu, Yingyun
    Zhou, Guixiang
    Li, Daojing
    Liu, Yusheng
    [J]. REPRODUCTIVE BIOMEDICINE ONLINE, 2017, 35 (03) : 305 - 310