Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Sci Rep. 2022 Oct 21;12(1):17664. doi: 10.1038/s41598-022-22687-y.
This study aims to identify genetic causes of familial female infertility characterized by embryonic developmental arrest (EDA) and repeated implantation failure (RIF) with oocyte donation IVF cycle. We used Whole-exome sequencing and Sanger validation to find causative genes in an Iranian consanguineous family that had 3 infertile daughters, 4 fertile daughters, and 2 fertile sons. All patients in this consanguineous family exhibited typical manifestations of unexplained RIF and EDA. Genetic analysis identified a homozygous missense variant (c.G1054C:p.G352R) in exon 13 of the TLE6 gene that cosegregated with the EDA phenotype in an autosomal recessive pattern. Other members of the family, the gene carriers, remain clinically asymptomatic and fertile. Our findings identify a novel nonsynonymous variant, c.G1054C:p.G352R, in the TLE6 gene within a consanguineous Iranian family with autosomal-recessive female infertility and broaden the genetic spectrum of TLE6-associated EDA.
本研究旨在鉴定卵母细胞捐赠 IVF 周期中表现为胚胎发育停滞（EDA）和反复着床失败（RIF）的家族性女性不育的遗传原因。我们使用全外显子组测序和 Sanger 验证在一个伊朗近亲家庭中发现了致病基因，该家庭有 3 个不育女儿、4 个可育女儿和 2 个可育儿子。这个近亲家庭的所有患者都表现出不明原因的 RIF 和 EDA 的典型表现。遗传分析确定了 TLE6 基因第 13 外显子中一个纯合错义变异（c.G1054C:p.G352R），该变异以常染色体隐性模式与 EDA 表型共分离。该家族的其他成员，即基因携带者，仍保持临床无症状和生育能力。我们的发现确定了一个新的非同义变异 c.G1054C:p.G352R，位于一个具有常染色体隐性女性不育的伊朗近亲家庭中的 TLE6 基因内，并扩大了 TLE6 相关 EDA 的遗传谱。
