CYP21A2基因复合杂合突变及多基因突变的男性无精症一例并文献复习

doi:10.12280/gjszjk.20220207

摘要/Abstract

摘要：

CYP21A2基因突变可引起21-羟化酶缺乏症,导致先天性肾上腺皮质增生症和性腺发育异常。根据CYP21A2基因突变位点不同,21-羟化酶缺乏症的临床表型存在异质性,成年患者常以生育障碍为首诊原因。CYP21A2基因突变同时合并多基因突变的复杂病例,国内外尚少见报道。报道1例CYP21A2基因c.518T>A/c.293-13A>G复合杂合突变的男性无精症病例,该患者合并DNAJB13/DNAI1/QRICH2J/FSIP2/HYDIN多基因突变,临床表型为男性不育症,经3个月糖皮质激素治疗后获得生精功能。该病例丰富了有关男性不育症的基因型,也为此类复合杂合基因突变疾病的诊治提供了临床经验。

关键词: CYP21A2基因, 21-羟化酶缺乏症, 无精子症, 突变, 病例报告

Abstract:

CYP21A2 mutation causes 21-hydroxylase deficiency (21-OHD), leading to congenital adrenal hyperplasia and gonadal dysplasia. There is heterogeneity in clinical phenotype due to the different gene mutation sites. Infertility appears to be the leading cause for adult 21-OHD outpatients. The complicated cases of the CYP21A2 mutation combined with multiple gene mutations were rarely reported in the worldwide. We reported a case of male azoospermia with the compound heterozygous mutation of c.518T>A/c.293-13A>G coding CYP21A2. Interestingly, this case was complicated with DNAJB13/DNAI1/QRICH2J/FSIP2/HYDIN multi-gene mutations. The clinical phenotype was male infertility, and spermatogenesis was established by the treatment with glucocorticoid for three months. This case report enriched the genotypes of male infertility, and provided us with experience in the clinical diagnosis and treatment of these diseases.

Key words: CYP21A2 gene, 21-hydroxylase deficiency, Azoospermia, Mutation, Case reports

龚一昕, 丁宇, 骆斯慧, 郑雪瑛. CYP21A2基因复合杂合突变及多基因突变的男性无精症一例并文献复习[J]. 国际生殖健康/计划生育, 2022, 41(4): 284-288.

GONG Yi-xin, DING Yu, LUO Si-hui, ZHENG Xue-ying. Male Azoospermia Caused by Compound Heterozygous Mutation in CYP21A2 Gene and Multi-Gene Mutations: A Case Report and Literature Review[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(4): 284-288.

图/表 3

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文献来源	临床分型	突变形式	治疗方案	干预结果
Scaroni等（2003）^[11]	SW型	/	口服DXM 1 mg/d（给药时间不详）	第7个月出现不活动精子
Claahsen-van der Grinten等（2007）^[12]	SV型	I1del/I12N	口服DXM 0.75 mg/d（分早中晚各1次给药）	第3个月精子数量增加,第7个月其妻妊娠
Collet等（2010）^[13]	SW型	/	口服DXM 0.5 mg bid,MC 0.05 mg bid	第12个月其妻分娩一男婴
Rohayem 等（2014）^[14]	SV型	g.655A/C>G	注射人绒毛膜促性腺激素1 500 IU biw,人绝经期促性腺激素150 IU tiw	第21个月精子数量增加,其妻自然妊娠,分娩一健康女婴
Tanaka 等（2017）^[15]	SV型	c.518T>A	口服DXM 0.5 mg/d（给药时间不详）	第2个月精子浓度34×10⁶/mL,2年后其妻体外受精妊娠,后分娩一健康婴儿
Jha 等（2019）^[16]	SW型	c.293-13A/C>G	口服泼尼松 5 mg qm,MC 50 μg bid,出现增重、失眠、腹部紫纹,更换泼尼松为DXM 0.25 mg qn	第9个月其妻自然妊娠,后分娩一女婴,女婴CYP21A2等位基因30 kb缺失
Fouques等（2019）^[17]	SW型	c.1160A>T	口服HC 25 mg qm,DXM 0.5 mg qn	第4个月精子数量增加,第6个月其妻自然妊娠,分娩健康女婴
	SW型	c.293-13A/C>G	口服HC 20 mg qm,HC 10 mg q12n,DXM 0.5 mg qn	第12个月精子数量仍为0
梁凯等（2018）^[18]	SV型	c.518T>A/c.955c>T	初始口服DXM 0.75 mg qd,自第4个月调整DXM用量为0.375 mg qd	第12个月精子数量仍为0
Bry-Gauillard等（2014）^[19]	SV型	/	口服米托坦3 g/d,维持7个月后减量为2 g/d	第8个月精子数量开始升高,第25个月时精子浓度4.5×10⁶/mL
Bachelot等（2021）^[20]	SW型	c.293-13A/C>G	口服米托坦 0.5 g/d	第12个月精子数量增加,12×10⁶/mL,2年后其妻分娩一健康婴儿

文献来源	临床分型	突变形式	治疗方案	干预结果
Scaroni等（2003）^[11]	SW型	/	口服DXM 1 mg/d（给药时间不详）	第7个月出现不活动精子
Claahsen-van der Grinten等（2007）^[12]	SV型	I1del/I12N	口服DXM 0.75 mg/d（分早中晚各1次给药）	第3个月精子数量增加,第7个月其妻妊娠
Collet等（2010）^[13]	SW型	/	口服DXM 0.5 mg bid,MC 0.05 mg bid	第12个月其妻分娩一男婴
Rohayem 等（2014）^[14]	SV型	g.655A/C>G	注射人绒毛膜促性腺激素1 500 IU biw,人绝经期促性腺激素150 IU tiw	第21个月精子数量增加,其妻自然妊娠,分娩一健康女婴
Tanaka 等（2017）^[15]	SV型	c.518T>A	口服DXM 0.5 mg/d（给药时间不详）	第2个月精子浓度34×10⁶/mL,2年后其妻体外受精妊娠,后分娩一健康婴儿
Jha 等（2019）^[16]	SW型	c.293-13A/C>G	口服泼尼松 5 mg qm,MC 50 μg bid,出现增重、失眠、腹部紫纹,更换泼尼松为DXM 0.25 mg qn	第9个月其妻自然妊娠,后分娩一女婴,女婴CYP21A2等位基因30 kb缺失
Fouques等（2019）^[17]	SW型	c.1160A>T	口服HC 25 mg qm,DXM 0.5 mg qn	第4个月精子数量增加,第6个月其妻自然妊娠,分娩健康女婴
	SW型	c.293-13A/C>G	口服HC 20 mg qm,HC 10 mg q12n,DXM 0.5 mg qn	第12个月精子数量仍为0
梁凯等（2018）^[18]	SV型	c.518T>A/c.955c>T	初始口服DXM 0.75 mg qd,自第4个月调整DXM用量为0.375 mg qd	第12个月精子数量仍为0
Bry-Gauillard等（2014）^[19]	SV型	/	口服米托坦3 g/d,维持7个月后减量为2 g/d	第8个月精子数量开始升高,第25个月时精子浓度4.5×10⁶/mL
Bachelot等（2021）^[20]	SW型	c.293-13A/C>G	口服米托坦 0.5 g/d	第12个月精子数量增加,12×10⁶/mL,2年后其妻分娩一健康婴儿