NR5A1基因突变的46,XY性发育异常合并肥胖及高胰岛素血症一例

doi:10.12280/gjfckx.20230049

摘要/Abstract

摘要：

46,XY性发育异常（disorders of sex development，DSD）是一种遗传学性别、表型性别和性腺性别不一致的先天性疾病，确诊该病的关键是基因检测。回顾分析1例46,XY DSD患者，患者社会性别为女性，因查体发现性腺发育异常就诊。患者46,XY DSD合并肥胖及高胰岛素血症，致病基因为类固醇生成因子-1（steroidogenic factor 1，SF-1，又称NR5A1），突变位点为c.1095_1096insTCGG（p.Q366Sfs*22），对该基因进行遗传学分析，该位点所致的基因突变可能与肥胖及糖尿病相关。行腹腔镜双侧隐睾切除术+外阴整形术+阴蒂切除术，维持患者女性社会性别。从遗传学角度检测病因可为46,XY DSD的临床诊治提供指导及依据。

关键词: 性发育障碍, 46,XY, 类固醇生成因子1, 突变, 儿童肥胖, 高胰岛素血症

Abstract:

46,XY disorders of sex development (DSD) are congenital disorder in which the genetic sex, phenotypic sex, and gonadal sex is inconsistent, and the key to confirming the diagnosis of the disorder is genetic testing. A retrospective analysis of a patient with 46,XY DSD, who was female by gender and was seen for abnormal gonadal development found on physical examination. The patient 46,XY DSD was combined with obesity and hyperinsulinemia, and the causative gene was steroidogenic factor 1 (SF-1 or NR5A1) with mutation locus c.1095_1096insTCGG (p.Q366Sfs*22), which was genetically analyzed, and the mutation due to this locus may be associated with obesity and diabetes mellitus. Perform laparoscopic bilateral cryptorchidism, vulvoplasty and clitoral resection to maintain the female gender of the patient. The detection of the cause from the genetic perspective may provide guidance and basis for the clinical management of 46,XY DSD.

Key words: Disorder of sex development, 46,XY, Steroidogenic factor 1, Mutation, Pediatric obesity, Hyperinsulinism

陈辰, 汤中云, 李敏, 张迎春. NR5A1基因突变的46,XY性发育异常合并肥胖及高胰岛素血症一例[J]. 国际妇产科学杂志, 2023, 50(3): 271-274.

CHEN Chen, TANG Zhong-yun, LI Min, ZHANG Ying-chun. NR5A1 Mutation in 46,XY Disorders of Sex Development Combined with Obesity and Hyperinsulinemia: A Case Report[J]. Journal of International Obstetrics and Gynecology, 2023, 50(3): 271-274.

图/表 3

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基因	染色体位置	转录本外显子	核苷酸及氨基酸变化	纯合/杂合	正常人频率	预测	致病性分析	疾病/表型（遗传方式）
CLCNKB	chr1:16377999	NM_000085;exon13	c.1254-1255del insTG (p.1419V)	het	-	-	临床意义未明变异	双等位基因Bartter综合征4B型（DR）；Bartter综合征3型（AR）
SLC26A4	chr7:107314680	NM_000441;exon5	c.487G>C (p.V163L)	het	0.000 199 7	LD	疑似致病性变异	Pendred综合征（AR）；常染色体隐性耳聋4型伴前庭导水管扩大（AR）
ABCA1	chr9:107620876	NM_005502;exon7	C.647G>A (p.G216D)	het	0.000 108 7	B	临床意义未明变异	高密度脂蛋白缺乏症（AR）；家族性高密度脂蛋白缺乏症（-）
ALMS1	chr2:73676377	NM_015120;exon8	c.2720A>C (p.Y907S)	het	-	B	临床意义未明变异	Alstrom综合征（AR）
SRD5A2	chr2:31754532	NM_000348;exon5	c547-5C>T (Splicing)	het	0.000 016 8	-	临床意义未明变异	类固醇5α-还原酶缺乏症（AR）
AGT	chr1:230838973	NM_001382817;exon5	c.1345C>T (p.R449C)	het	0.001 925 6	LD	临床意义未明变异	肾小管发育不全（AR）；高血压易感型（Mu）
IGFALS	chr16:1842398	NM_004970;exon2	c.21C>G	het	0.000 199 7	-	临床意义未明变异	酸稳定性亚单位缺乏症（-）
KMT2D	chr12:49434871	NM_003482;exon32	c.6682A>G (p.T2228A)	hom	0.000 701 4	B	临床意义未明变异	歌舞伎综合征1型（AD）
HPRT1	chrX:133634054- 133634055	NM_000194;exon9	c.610-5delT (splicing)	hemi	0.004 100 0	-	临床意义未明变异	Lesch-Nyhan综合征（XLR）；Kelley-Seegmiller综合征（XLR）

基因	染色体位置	转录本外显子	核苷酸及氨基酸变化	纯合/杂合	正常人频率	预测	致病性分析	疾病/表型（遗传方式）
CLCNKB	chr1:16377999	NM_000085;exon13	c.1254-1255del insTG (p.1419V)	het	-	-	临床意义未明变异	双等位基因Bartter综合征4B型（DR）；Bartter综合征3型（AR）
SLC26A4	chr7:107314680	NM_000441;exon5	c.487G>C (p.V163L)	het	0.000 199 7	LD	疑似致病性变异	Pendred综合征（AR）；常染色体隐性耳聋4型伴前庭导水管扩大（AR）
ABCA1	chr9:107620876	NM_005502;exon7	C.647G>A (p.G216D)	het	0.000 108 7	B	临床意义未明变异	高密度脂蛋白缺乏症（AR）；家族性高密度脂蛋白缺乏症（-）
ALMS1	chr2:73676377	NM_015120;exon8	c.2720A>C (p.Y907S)	het	-	B	临床意义未明变异	Alstrom综合征（AR）
SRD5A2	chr2:31754532	NM_000348;exon5	c547-5C>T (Splicing)	het	0.000 016 8	-	临床意义未明变异	类固醇5α-还原酶缺乏症（AR）
AGT	chr1:230838973	NM_001382817;exon5	c.1345C>T (p.R449C)	het	0.001 925 6	LD	临床意义未明变异	肾小管发育不全（AR）；高血压易感型（Mu）
IGFALS	chr16:1842398	NM_004970;exon2	c.21C>G	het	0.000 199 7	-	临床意义未明变异	酸稳定性亚单位缺乏症（-）
KMT2D	chr12:49434871	NM_003482;exon32	c.6682A>G (p.T2228A)	hom	0.000 701 4	B	临床意义未明变异	歌舞伎综合征1型（AD）
HPRT1	chrX:133634054- 133634055	NM_000194;exon9	c.610-5delT (splicing)	hemi	0.004 100 0	-	临床意义未明变异	Lesch-Nyhan综合征（XLR）；Kelley-Seegmiller综合征（XLR）