Case Report: Neo-homozygous nonsense mutation in NLRP5 associated with early embryonic arrest in two sisters from a Chinese family

Early embryonic arrest (EEA) can result in repeated failures of assisted reproductive technology, with genetic variation being the primary cause. The maternal protein nucleotide-binding oligomerization domain-like receptor protein 5 (NLRP5) plays a role in oocyte maturation and embryonic development before the blastocyst stage. Mutations in the NLRP5 gene can lead to various reproductive outcomes, including oocyte maturation disorder, fertilization failure, and EEA. We discovered a new homozygous nonsense mutation (c.779G > A; p.Trp260*) in NLRP5 in two sisters from a Chinese family. This clinically presented as halted embryonic development at the 2-7 cell stage. The parents and brother were heterozygous carriers and exhibited normal fertility, indicating that the pathogenic gene was inherited in an autosomal recessive manner. Analyses revealed significantly decreased expression of NLRP5 at the 3' end of the mRNA and the C-terminal of the protein <i>in vitro</i> (<i>p</i> < 0.05). This suggests that NLRP5 protein dysfunction is the primary cause of EEA in this case. Additionally, the expression levels are inconsistent with those of previous studies, indicating that different mutation sites lead to variations in NLRP5 protein expression and distinct pathogenic mechanisms. Our finding expands the spectrum of pathogenic variants in EEA caused by the NLRP5 gene.