RT Journal Article
SR Electronic
T1 Mutations in <em>NLRP2</em> and <em>NLRP5</em> cause female infertility characterised by early embryonic arrest
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 471
OP 480
DO 10.1136/jmedgenet-2018-105936
VO 56
IS 7
A1 Mu, Jian
A1 Wang, Wenjing
A1 Chen, Biaobang
A1 Wu, Ling
A1 Li, Bin
A1 Mao, Xiaoyan
A1 Zhang, Zhihua
A1 Fu, Jing
A1 Kuang, Yanping
A1 Sun, Xiaoxi
A1 Li, Qiaoli
A1 Jin, Li
A1 He, Lin
A1 Sang, Qing
A1 Wang, Lei
YR 2019
UL http://jmg.bmj.com/content/56/7/471.abstract
AB Background Successful human reproduction requires normal spermatogenesis, oogenesis, fertilisation and early embryonic development, and abnormalities in any of these processes will result in infertility. Early embryonic arrest is commonly observed in infertile patients with recurrent failure of assisted reproductive technology (ART). However, the genetic basis for early embryonic arrest is largely unknown.Objective We aim to identify genetic causes of infertile patients characterised by early embryonic arrest.Methods We pursued exome sequencing in a proband with embryonic arrest from the consanguineous family. We further screened candidate genes in a cohort of 496 individuals diagnosed with early embryonic arrest by Sanger sequencing. Effects of mutations were investigated in HeLa cells, oocytes and embryos.Results We identified five independent individuals carrying biallelic mutations in NLRP2. We also found three individuals from two families carrying biallelic mutations in NLRP5. These mutations in NLRP2 and NLRP5 caused decreased protein expression in vitro and in oocytes and embryos.Conclusions NLRP2 and NLRP5 are novel mutant genes responsible for human early embryonic arrest. This finding provides additional potential diagnostic markers for patients with recurrent failure of ART and helps us to better understand the genetic basis of female infertility characterised by early embryonic arrest.