Novel mutations in NLRP5 and PATL2 cause female infertility characterized by primarily oocyte maturation abnormality and consequent early embryonic arrest
Novel mutations in NLRP5 and PATL2 cause female infertility characterized by primarily oocyte maturation abnormality and consequent early embryonic arrest
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NLRP5 和 PATL2 的新突变导致女性不孕，其主要特征是卵母细胞成熟异常和随后的早期胚胎停滞
DOI：
10.1007/s10815-022-02412-4
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发表时间：
2022-01-28
影响因子：
3.1
通讯作者：
Tong, Xianhong
中科院分区：
文献类型：
--
作者：
Huang, Lingli;Wang, Yu;Tong, Xianhong
本研究旨在确定12例原发性不孕症的遗传原因，其特征是主要的卵母细胞成熟异常和随后的早期胚胎停滞。从外周血样品中分离基因组DNA。对先证者进行全外显子组测序，并通过桑格测序确认鉴定的变体。通过计算机模拟评估蛋白质上鉴定的变体的致病性。并采用qRT-PCR方法检测新突变对NLRP 5 mRNA水平的影响。NLRP 5中的新型纯合移码变体（p.V429Efs*30）和具有新型移码变体（p.A297Efs*20）和复发变体（c. 223-14_223-2delCCCTCCTGTTCCA）。qRT-PCR显示突变型NLRP 5 mRNA表达明显降低。此外，NLRP 5和PATL 2的截短蛋白被预测为无功能的，这是由于分别缺失了关键功能结构域的大部分或整个区域。这项研究确定了NLRP 5和PATL 2的新突变，进一步扩大了这两个基因的突变和表型谱。这是首次报道与人类卵母细胞成熟异常相关的NLRP 5突变。
This study aims to identify the genetic causes of 12 women with primary infertility characterized by primarily oocyte maturation abnormality and consequent early embryonic arrest. Genomic DNA was isolated from peripheral blood samples. Whole-exome sequencing was performed on the probands, and the identified variants were confirmed by Sanger sequencing. The pathogenicity of the identified variants on the protein was accessed in silico. And we used qRT-PCR to detect the possible effects of the novel mutation on the mRNA level of NLRP5. A novel homozygous frameshift variant (p.V429Efs*30) in NLRP5 and compound heterozygous variants with a novel frameshift variant (p.A297Efs*20) and a recurrent variant (c. 223-14_223-2delCCCTCCTGTTCCA) in PATL2 were identified in two unrelated affected individuals. qRT-PCR showed an obvious decrease of the mutant NLRP5 mRNA. In addition, the truncated proteins of NLRP5 and PATL2 were predicted to be non-functional due to the deletion of the most or the whole region of the critical functional domain(s) respectively. This study identified novel mutations in NLRP5 and PATL2, further expanding the mutational and phenotypic spectrum of both genes. This is the first report of the NLRP5 mutations that associates with oocyte maturation abnormality in humans.