Paris Descartes University, Gynecology Endocrinology Unit, Port-Royal Teaching Hospital, AP-HP, Paris, France.
Paris Diderot University, Sorbonne Paris Cité, U1141, Inserm, Paris, France.
J Clin Endocrinol Metab. 2018 Dec 1;103(12):4482-4490. doi: 10.1210/jc.2018-00410.
Mutations in the kisspeptin receptor (KISS1R) gene have been reported in a few patients with normosmic congenital hypogonadotropic hypogonadism (nCHH) (OMIM #146110).
To describe a female patient with nCHH and a novel homozygous KISS1R mutation and to assess the role of kisspeptin pathway to induce an ovulation by GnRH pulse therapy.
DESIGN, SETTING, AND INTERVENTION: Observational study of a patient including genetic and kisspeptin receptor functions and treatment efficiency using a GnRH pump.
Response to pulsatile GnRH therapy.
A partial isolated gonadotropic deficiency was diagnosed in a 28-year-old woman with primary amenorrhea and no breast development. A novel homozygous c.953T>C variant was identified in KISS1R. This mutation led to substitution of leucine 318 for proline (p.Leu318Pro) in the seventh transmembrane domain of KISS1R. Signaling via the mutated receptor was profoundly impaired in HEK293-transfected cells. The mutated receptor was not detected on the membrane of HEK293-transfected cells. After several pulsatile GnRH therapy cycles, an LH surge with ovulation and pregnancy was obtained.
GnRH pulsatile therapy can induce an LH surge in a woman with a mutated KISS1R, which was previously thought to be completely inactivated in vivo.
已经有少数嗅觉正常的先天性促性腺激素低下性性腺功能减退症（nCHH）（OMIM#146110）患者的 kisspeptin 受体（KISS1R）基因发生突变。
描述一名患有 nCHH 的女性患者，该患者携带一种新的纯合 KISS1R 突变，并评估 kisspeptin 通路在 GnRH 脉冲治疗诱导排卵中的作用。
设计、设置和干预：对一名患者进行遗传和 kisspeptin 受体功能以及使用 GnRH 泵治疗效率的观察性研究。
对 GnRH 脉冲治疗的反应。
一名 28 岁的原发性闭经且无乳房发育的女性患者被诊断为部分孤立性促性腺激素缺乏症。在 KISS1R 中发现了一种新的纯合 c.953T>C 变异，导致第七跨膜结构域中亮氨酸 318 被脯氨酸取代（p.Leu318Pro）。突变受体在转染 HEK293 细胞中的信号转导受到严重损害。突变受体未在转染 HEK293 细胞的细胞膜上检测到。经过几个 GnRH 脉冲治疗周期后，获得了 LH 激增和排卵妊娠。
GnRH 脉冲治疗可诱导突变 KISS1R 女性的 LH 激增，此前认为该受体在体内完全失活。
