一例NSMF基因突变所致特发性低促性腺激素性性功能减退症的诊治分析

doi:10.16288/j.yczz.25-187

遗传 ›› 2026, Vol. 48 ›› Issue (5): 535-543.doi: 10.16288/j.yczz.25-187

一例NSMF基因突变所致特发性低促性腺激素性性功能减退症的诊治分析

彭书仪(), 王恺, 汪舒琪, 张铭津, 盛沛, 安晓飞()

南京中医药大学附属医院，南京 210029

收稿日期:2025-11-04 修回日期:2026-01-13 出版日期:2026-02-09 发布日期:2026-02-09
通讯作者: 安晓飞，医学博士，主任医师，研究方向：代谢内分泌疾病的中西医临床研究。E-mail: anxiaofei2000@163.com
作者简介:彭书仪，硕士研究生，专业方向：代谢内分泌疾病的中西医临床研究。E-mail: yunche0220@163.com
基金资助:
国家自然科学基金项目(82374386)

Diagnosis and treatment analysis of a case of idiopathic hypogonadotropic hypogonadism caused by NSMF gene mutation

Shuyi Peng(), Kai Wang, Shuqi Wang, Mingjin Zhang, Pei Sheng, Xiaofei An()

Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China

Received:2025-11-04 Revised:2026-01-13 Published:2026-02-09 Online:2026-02-09
Supported by:
National Natural Science Foundation of China(82374386)

摘要/Abstract

摘要：

特发性低促性腺激素性性功能减退症(idiopathic hypogonadotropic hypogonadism，IHH)是一种以内源性促性腺激素释放激素(gonadotropin-releasing hormone，GnRH)缺乏或作用缺陷为特征的罕见内分泌疾病，主要临床表现为性腺功能障碍。IHH患者根据是否合并嗅觉障碍分为两大类：伴有嗅觉受损者称为卡尔曼综合征(Kallmann syndrome，KS)，嗅觉正常者称为嗅觉正常的IHH (normosmic IHH，nIHH)。本文报道了1例15岁男性，表现为第二性征发育迟缓，相关检查提示存在低促性腺激素水平的低睾酮血症且嗅觉正常，诊断为nIHH。高通量基因测序提示该患者存在NSMF:c.79C>G(p.Arg27Gly)基因突变，该突变位点在既往国内外文献中尚未报道。通过总结该患者临床特点及对NSMF基因新变异进行分析，丰富了NSMF基因变异谱，并为该类疾病的临床精准诊疗提供了临床资料和遗传资源。

关键词: 特发性低促性腺激素性性功能减退症, 低睾酮血症, NSMF基因

Abstract:

Idiopathic hypogonadotropic hypogonadism (IHH) is a rare endocrine disorder characterized by deficiency or dysfunction of endogenous gonadotropin-releasing hormone (GnRH), leading primarily to hypogonadism. Based on the presence or absence of olfactory dysfunction, IHH is classified into Kallmann syndrome (KS) and normosmic IHH (nIHH). In this study, we reported a 15-year-old male with nIHH, presenting with delayed puberty, hypogonadotropic hypogonadism and normal olfaction. High-throughput gene sequencing identified a novel NSMF:c.79C>G (p.Arg27Gly) variant which has not been reported in the previous literature. By summarizing the patient’s clinical characteristics and analyzing new NSMF gene variant, this study enriches the mutation spectrum of NSMF gene and provides clinical data and genetic resources for the diagnosis and treatment of IHH.

Key words: idiopathic hypogonadotropic hypogonadism, hypotestosteronism, NSMF gene

彭书仪, 王恺, 汪舒琪, 张铭津, 盛沛, 安晓飞. 一例NSMF基因突变所致特发性低促性腺激素性性功能减退症的诊治分析[J]. 遗传, 2026, 48(5): 535-543.

Shuyi Peng, Kai Wang, Shuqi Wang, Mingjin Zhang, Pei Sheng, Xiaofei An. Diagnosis and treatment analysis of a case of idiopathic hypogonadotropic hypogonadism caused by NSMF gene mutation[J]. Hereditas(Beijing), 2026, 48(5): 535-543.

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病例	性别	核苷酸变异	氨基酸改变	结构域	共存突变基因	遗传模式	表型类型	参考文献
1	男	c.1261C>T	p.Leu421Phe	ZFD	PROKR2、 SPRY4	寡基因遗传	KS	[25]
2	男	c.C53A	p.Ser18X	-	-	单基因遗传	IHH	[26]
3	男	c.1025G>T	p.Gly342Val	-	-	单基因遗传	FHH	[27]
4	男	-	-	-	-	单基因遗传	IHH	[28]
5	男	c.533C > A	p.Thr178Asn	-	CHD7	寡基因遗传	nIHH	[11]
6	男	c.421G > A	p.Ala141Thr	ZFD	ANOS1	寡基因遗传	KS	[11]
7	男	c.241G > A	p.Gly81Ser	-	-	单基因遗传	KS	[11]
8	男	c.521C > T	p.Ala174Val	-	-	单基因遗传	KS	[11]
9	男	c.500G>A	p.Cys167Tyr	ZFD	BMP2	寡基因遗传	nIHH	[6]
10	男	c.909C>T	p.His303=	-	-	单基因遗传	nIHH	[6]
11	男	c.497A>G	p.Glu166Gly	ZFD	FGF8	寡基因遗传	nIHH	[6]
12	男	c.365_366insA	p.Val123GlyfsTer69	-	-	单基因遗传	nIHH	[6]
13	男	c.757G>A	p.Ala253Thr	-	KAL1	寡基因遗传	KS	[17]
14	男	c.1160-13C>T	-	-	TACR3	寡基因遗传	KS	[17]
15	男	c.629-21G>C;c.629-23C>G	-	-	-	单基因遗传	nIHH	[17]
16	男	c.1438 A>G，	p.Thr480 Ala	NES	-	单基因遗传	IHH	[29]

一例NSMF基因突变所致特发性低促性腺激素性性功能减退症的诊治分析

Diagnosis and treatment analysis of a case of idiopathic hypogonadotropic hypogonadism caused by NSMF gene mutation

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