Center of Reproductive Medicine, Affiliated Hospital of Medical School, Jinling Hospital, Southeast University, Nanjing, 210002, Jiangsu, China.
Center of Reproductive Medicine, Affiliated Hospital of Medical School, Jinling Hospital, Nanjing University, Nanjing, 21002, Jiangsu, China.
J Assist Reprod Genet. 2023 Dec;40(12):2945-2950. doi: 10.1007/s10815-023-02961-2. Epub 2023 Oct 7.
A 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.
Genomic 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.
One 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.
We 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.
一名 32 岁女性被诊断为原因不明的原发性不孕症 10 年。她的基础激素水平大致正常，但基础卵泡刺激素（FSH）水平升高。此外，抗苗勒管激素水平处于正常范围内，并且她已经经历了两次失败的卵母细胞采集尝试。我们旨在研究卵巢卵泡发生受损患者的女性不育遗传原因。
从患者及其家庭成员的外周血中提取基因组 DNA。对患者进行全外显子组测序，并通过 Sanger 测序鉴定和确认 TBPL2 突变。使用 Exome Aggregation Consortium（ExAC）Browser 和 Genome Aggregation Database（gnomAD）Browser Beta 在普通人群中搜索变体的等位基因频率。使用 SIFT、Mutation Taster 和 CADD 软件分析突变的危害性。
在不育家族中发现了 TBPL2 中的一个新突变 c.802C>T（p.Arg268Ter）和一个已知变体 c.788+3A>G（p.Arg233Ter）。TBPL2 中的复合杂合突变可能是卵巢卵泡发生受损、超排卵失败和不孕的原因。
我们鉴定了 TBPL2 中的复合杂合突变，这些突变导致患者的卵巢卵泡发生受损、超排卵失败和不孕。这些发现表明 TBPL2 中的复合杂合突变具有重要作用，并扩展了 TBPL2 的突变谱，这可能为女性不孕提供新的精确诊断标志物。
