Chen Xiaoqian, Hu Man, Du Tingting, Yang Luhong, Li Yakun, Feng Lifang, Luo Juan, Yao Hui, Chen Xiaohong
Department of Endocrinology and Metabolism, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Pediatr Endocrinol Metab. 2024 Sep 13;37(11):999-1008. doi: 10.1515/jpem-2024-0119. Print 2024 Nov 26.
Congenital hypogonadotropic hypogonadism (CHH) is a rare condition caused by a defect in the production, secretion or action of gonadotropin-releasing hormone. The absence of puberty and varying degrees of gonadotropic deficiency are common symptoms of this disorder. Heterogeneity exists in the clinical presentation of the different clinical subtypes and multiple genes have been implicated in CHH. A number of genetic defects have been identified as causes normosmic CHH, including mutations of , , , , and . Loss-of-function mutations in gene are a rare cause of normosmic CHH.
We described an 11.5 years old Chinese patient who presented at birth with micropenis, microorchidia and bilateral cryptorchidism. Whole-exome sequencing was also performed and identified a homozygous mutation of gene, c.1010_1028del (p.V337Afs*82). The variant was predicted as "deleterious" and classified as "likely pathogenic". This variant has never been reported in patients with CHH. Furthermore, we summarized the clinical presentations and analyzed the phenotype-genotype correlation between CHH and mutations in previous reports.
This study details the clinical phenotypes and hormone levels of the patient and expands the spectrum of mutations in the gene associated with CHH.
先天性低促性腺激素性性腺功能减退症（CHH）是一种由促性腺激素释放激素产生、分泌或作用缺陷引起的罕见病症。青春期缺失和不同程度的促性腺激素缺乏是该疾病的常见症状。不同临床亚型的临床表现存在异质性，且多个基因与CHH有关。已确定多种遗传缺陷是嗅觉正常的CHH的病因，包括 、 、 、 、 和 的突变。 基因的功能丧失突变是嗅觉正常的CHH的罕见病因。
我们描述了一名11.5岁的中国患者，其出生时表现为小阴茎、小睾丸和双侧隐睾。还进行了全外显子组测序，鉴定出 基因的纯合突变，即c.1010_1028del（p.V337Afs*82）。该变异被预测为“有害”，并被分类为“可能致病”。该变异在CHH患者中从未被报道过。此外，我们总结了临床表现，并分析了先前报道中CHH与 突变之间的表型-基因型相关性。
本研究详细描述了患者的临床表型和激素水平，并扩展了与CHH相关的 基因突变谱。
