Mutations in NLRP2 and NLRP5 cause female infertility characterised by early embryonic arrest
J Mu, W Wang, B Chen, L Wu, B Li, X Mao… - Journal of Medical …, 2019 - jmg.bmj.com
J Mu, W Wang, B Chen, L Wu, B Li, X Mao, Z Zhang, J Fu, Y Kuang, X Sun, Q Li, L Jin, L He…
Journal of Medical Genetics, 2019•jmg.bmj.comBackground 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 …
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 …
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.
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