Compound heterozygous mutations in TBPL2 were identified in an infertile woman with impaired ovarian folliculogenesis
Compound heterozygous mutations in TBPL2 were identified in an infertile woman with impaired ovarian folliculogenesis
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DOI：
10.1007/s10815-023-02961-2
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发表时间：
2023-10
影响因子：
3.1
通讯作者：
Tian Du;Meiling Li;Li Chen;Yong Shao;Yichun Wang;Hui Wang;Jinzhao Ma;Bing Yao
中科院分区：
文献类型：
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作者：
Tian Du;Meiling Li;Li Chen;Yong Shao;Yichun Wang;Hui Wang;Jinzhao Ma;Bing Yao
一位32岁女性被诊断为不明原因的原发性不孕症10年。她的基础激素水平大致正常，但她的基础卵泡刺激素（FSH）水平升高。此外，抗苗勒管激素水平在正常范围内，她经历了两次失败的卵母细胞收集尝试。我们的目的是探讨女性不孕症患者的遗传原因与卵巢卵泡发育受损。方法基因组DNA提取患者及其家庭成员的外周血。对患者进行全外显子组测序，并通过桑格测序鉴定和确认TBPL 2突变。使用外显子组聚合联盟（ExAC）浏览器和基因组聚合数据库（gnomAD）浏览器Beta来搜索一般群体中变体的等位基因频率。结果在该不育家系中发现了一个新的TBPL 2突变c.802C > T（p.Arg268Ter）和一个已知的突变c.788 + 3A > G（p.Arg233Ter）。复合杂合突变TBPL2可能是受损的卵巢folliculogenesis，失败的超排卵，和infertility.ConclusionsWe确定复合杂合突变TBPL2，导致受损的卵巢folliculogenesis，失败的超排卵，和不孕症的患者。这些结果提示TBPL 2复合杂合突变具有重要作用，并扩展了TBPL 2的突变谱，可能为女性不孕症提供一种新的精确诊断标志物。
ObjectiveA 32-year-old female was diagnosed with unexplained primary infertility for 10 years. She had roughly normal basal hormone levels, but her basal follicle-stimulating hormone (FSH) levels were elevated. In addition, the level of anti-Mullerian hormone was within the normal range, and she had undergone two failed oocyte collection attempts. We aimed to investigate the genetic cause of female infertility in patients with impaired ovarian folliculogenesis.MethodsGenomic DNA was extracted from the peripheral blood of the patient and her family members. Whole-exome sequencing was performed on the patient, and TBPL2 mutations were identified and confirmed by Sanger sequencing. The Exome Aggregation Consortium (ExAC) Browser and Genome Aggregation Database (gnomAD) Browser Beta were used to search the allele frequencies of the variants in the general population. The harmfulness of the mutations was analyzed by SIFT, Mutation Taster, and CADD software.ResultOne novel mutation, c.802C > T (p. Arg268Ter), and one known variant, c.788 + 3A > G (p. Arg233Ter), in TBPL2 were identified in the infertile family. Compound heterozygous mutations in TBPL2 may be the cause of impaired ovarian folliculogenesis, failure of superovulation, and infertility.ConclusionsWe identified compound heterozygous mutations in TBPL2 that caused impaired ovarian folliculogenesis, failure of superovulation, and infertility in patients. These findings suggest an important role for compound heterozygous mutations in TBPL2 and expand the mutational spectrum of TBPL2, which might provide a new precise diagnostic marker for female infertility.