Novel mutations in PATL2: expanding the mutational spectrum and corresponding phenotypic variability associated with female infertility
Novel mutations in PATL2: expanding the mutational spectrum and corresponding phenotypic variability associated with female infertility
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PATL2 的新突变：扩大与女性不孕相关的突变谱和相应的表型变异
DOI：
10.1038/s10038-019-0568-6
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发表时间：
2019-05-01
影响因子：
3.5
通讯作者：
Sang, Qing
中科院分区：
文献类型：
--
作者：
Wu, Ling;Chen, Hua;Sang, Qing
卵母细胞成熟停滞导致原发性女性不育，但这种表型的遗传病因仍不清楚。在此之前，我们和其他研究小组已经报道了PATL2中的双等位基因突变主要是人类卵母细胞生殖囊泡期停滞的原因，并且不同突变的特异性表型不同。在这里，我们发现了四个新的错义突变，（p.V260M、p.Q300*、p.T425P和p.D293Y），一种新的移码突变（p.N239Tfs*9），和一个报告的剪接突变（p.R75Vfs*21）在来自五个无关家族的七个受影响个体中的PATL2中，显示出卵母细胞成熟停滞、受精失败或胚胎发育停滞的多种表型，这进一步扩大了PALTL2突变患者的突变和表型谱。这项工作进一步表明了PATL2在卵母细胞成熟和早期胚胎发育中的关键作用，并将为确定PALT 2中的遗传变异作为辅助生殖技术评价卵母细胞和胚胎质量的额外标准提供基础。
Oocyte maturation arrest results in primary female infertility, but the genetic etiology of this phenotype remains largely unknown. Previously, we and other groups have reported that biallelic mutations in PATL2 are mainly responsible for human oocyte germinal vesicle-stage arrest and that the specific phenotype varies for different mutations. Here, we identified four novel missense mutations (p.V260M, p.Q300*, p.T425P, and p.D293Y), a novel frameshift mutation (p.N239Tfs*9), and a reported splicing mutation (p.R75Vfs*21) in PATL2 in seven affected individuals from five unrelated families, showing a multiplicity of phenotypes in oocyte maturation arrest, fertilization failure, or embryonic developmental arrest, which further expands the mutational and phenotypic spectrum in patients with PALTL2 mutations. This work further indicates the critical role of PATL2 in oocyte maturation and early embryo development and will provide a basis for pursuing the determination of genetic variation in PALT2 as an additional criterion for evaluating the quality of oocytes and embryos for assisted reproduction techniques.