一例SOX10基因缺失所致的Waardenburg综合征2型合并低促性腺激素性性腺功能减退症的诊断和基因检测分析

doi:10.16288/j.yczz.22-161

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Hereditas(Beijing) ›› 2022, Vol. 44 ›› Issue (12): 1158-1166.doi: 10.16288/j.yczz.22-161

• Genetic Resource • Previous Articles Next Articles

Diagnosis and genetic analysis of a case of Waardenburg syndrome type 2 with hypogonadotropic hypogonadism caused by SOX10 gene deletion

Siqi Wang(), Yang Chen, Kuanhong Luo, Ningjie Shi, Kangli Xiao, Zhenhai Cui, Tianshu Zeng, Huiqing Li()

Department of Endocrinology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430000, China

Received:2022-07-31 Revised:2022-09-21 Online:2022-12-20 Published:2022-10-09
Contact: Li Huiqing E-mail:wangsiqi8958@163.com;lhqing5@126.com

Abstract

Abstract:

Hypogonadotropic hypogonadism (HH) is a disease defined by dysfunction of the hypothalamic- pituitary-gonadal hormone axis, leading to low sex hormone levels and impaired fertility. HH with anosmia or hyposmia is known as Kallmann syndrome (KS). Waardenburg syndrome (WS) is a rare autosomal dominant genetic disorder characterized by sensorineural hearing loss and abnormal pigmentation. In this report, we collected the clinical data of a patient with hypogonadotropic hypogonadism and congenital hearing loss of unknown cause. The patient had no obvious secondary sexual characteristics development after puberty, and had a heterozygous deletion (at least 419 kb) in 22q13.1 region (Chr.22:38106433-38525560), which covered the SOX10 gene. The abnormalities were not found in gene sequencing analysis of both the parents and sister of the proband. By summarizing and analyzing the characteristics of this case, we further discussed the molecular biological etiological association between HH and WS type 2. This case also enriches the clinical data of subsequent genetic studies, and provides a reference for the diagnosis and treatment of such diseases.

Key words: Waardenburg syndrome, hypogonadotropic hypogonadism, Kallmann syndrome, SOX10 gene, mutation

Siqi Wang, Yang Chen, Kuanhong Luo, Ningjie Shi, Kangli Xiao, Zhenhai Cui, Tianshu Zeng, Huiqing Li. Diagnosis and genetic analysis of a case of Waardenburg syndrome type 2 with hypogonadotropic hypogonadism caused by SOX10 gene deletion[J]. Hereditas(Beijing), 2022, 44(12): 1158-1166.

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References 30

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基本特征与实验室检查	结果				参考范围
性别	男				—
年龄	18				—
身高/cm	171				—
体重/kg	44				—
性激素
促黄体生成素(IU/L)	2.6				1.7~8.6
促卵泡生成素(IU/L)	2.45				1.5~12.4
泌乳素(ng/mL)	11.61				2.7~15.2
孕酮(ng/mL)	0.11				<0.149
雌二醇(pg/mL)	<5.00				11.3~43.2
睾酮(nmol/L)	0.81				Tanner 5期：6.5~30.6
戈那瑞林兴奋实验	基础值		峰值
促卵泡生成素(IU/L)	1.63		5.01		FSH增加0.5~2倍
促黄体生成素(IU/L)	1.40		12.67		LH峰值升高>5倍
睾酮(ng/mL)	0.62
人绒毛膜促性腺激素兴奋实验	实验前		注射HCG 3天后
睾酮(ng/mL)	0.51		8.26		注射HCG后，睾酮平均增加0.5~2倍
甲状腺激素
FT3(pmol/L)	4.5				3.47~10.43
FT4(pmol/L)	12.9				11.2~20.1
TSH(μIU/mL)	3.11				0.34~5.06
	8 am	4 pm		12 pm
皮质醇(μg/L)	57.35	41.0		9.65	—
促肾上腺皮质激素(pg/mL)	57.35	9.65		28.16	—
胰岛素样生长因子-1(ng/mL)	1210.52				12岁：143~693；成人：141~483
左手骨龄片	13				—

病例	年龄	性别	自发性青春期	嗅觉	听力损失	其他临床症状	核苷酸变异	氨基酸改变	参考文献
1	26	男	无	缺失	单侧	白发，隐睾症	c.2T>G	p.?	[4]
2	18	女	无	缺失	双侧	上睑下垂	c.331T>G	p.Phe111Val	[4]
3	39	女	无	缺失	双侧	肥胖	c.424T>C	p.Trp142Arg	[4]
4	25	女	延迟	缺失	双侧	—	c.698-1G>C	p.spl?	[4]
5	20	男	延迟	缺失	双侧	隐睾症	c.1290del	p.Ser431Argfs*71	[4]
6	20	男	未描述	缺失	正常	智力障碍，先天畸形	c.1298G>A	p.Arg433Gln	[4]
7	33	男	无	缺失	双侧	上睑下垂	c.323T>C	p.Met108Trh	[4]
8	19	女	无	缺失	正常	巨腿畸形	c.451C>T	p.Arg151Cys	[4]
9	25	男	延迟	缺失	双侧	上睑下垂,隐睾症	c.122G>T	p.Gly41Val	[11]
10	20	男	延迟	缺失	正常	—	c.131C>G	p.Ala44Gly	[11]
11	38	男	延迟	缺失	单侧	—	c.238C>G	p.Leu80Val	[11]
12	17	男	延迟	缺失	双侧	灰白发，鼻根宽大	c.184G>T	p.Glu62X	[12]
13	13	女	延迟	缺失	双侧	额前白发，虹膜色素缺失	c.506delC	p.Pro169fsX117	[13]
14	15	男	延迟	缺失	双侧	蓝色虹膜	c.434T>C	p.Leu145Pro	[7]
15	30	男	延迟	缺失	双侧	虹膜色素缺失，甲亢	c.565G>T	p.Phe189X	[14]
16	17	男	无	缺失	双侧	虹膜色素缺失	c.373C>T	p.Glu125X	[8]
17	15	女	无	缺失	双侧	虹膜色素缺失，先天性巨结肠	c.124delC	p.Leu42Cysfs*67	[6]
18	25	男	无	缺失	双侧	—	c.475C>T	p.Arg159Trp	[15]
19	18	男	无	减退	双侧	额前白发，虹膜色素缺失	22q13.1微缺失	—

Diagnosis and genetic analysis of a case of Waardenburg syndrome type 2 with hypogonadotropic hypogonadism caused by SOX10 gene deletion

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