Advances in genetic research of congenital hypothyroidism in China

doi:10.7499/j.issn.1008-8830.2018.03.015

. 2018 Mar 25;20(3):243–250. [Article in Chinese] doi: 10.7499/j.issn.1008-8830.2018.03.015

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中国儿童先天性甲状腺功能减退症的基因学研究进展

Editor: Xiao-Song QIN¹

Reviewed by: Xiao-Yu CHEN¹, Xiao-Yu CHEN¹

PMCID: PMC7389777 PMID: 29530127

Abstract

先天性甲状腺功能减退症(先天性甲减)是新生儿最常见的一种内分泌障碍性疾病, 是由于甲状腺激素的合成不足而不能满足机体的需求。其发病机制主要分为两种, 即甲状腺发育不全和甲状腺内分泌障碍, 均可引起甲状腺激素合成过程中相关酶的缺陷而导致甲状腺激素合成不足。近年许多研究者在先天性甲减的基因学方面开展了广泛研究, 本文就已发现的与中国人先天性甲减相关的基因学研究进行综述。

Keywords: 先天性甲状腺功能减退症, 基因型, 表现型, 儿童

先天性甲状腺功能减低症(简称先天性甲减)是儿童最常见的先天性内分泌紊乱, 每3 000~4 000个新生儿就有一人发病^[1]。先天性甲减最主要的两种发病机制分别是甲状腺发育不全和甲状腺内分泌障碍。由甲状腺发育不全引起的约占85%~90%, 表现为甲状腺发育不良、甲状腺机能缺失及甲状腺异位等, 大部分为散发, 约5%的病例是家族性的^[2]。由甲状腺内分泌障碍引起的先天性甲减约占10%~15%, 主要是碘化物有机化缺陷导致甲状腺激素合成障碍。除此之外, 中枢性先天性甲减及甲状腺或靶器官反应低下也可以导致先天性甲减的发生。

部分先天性甲减是家族性的, 提示其发病可能与遗传因素有关。目前研究者已通过二代测序等技术发现了多种与先天性甲减有关的候选基因。

1. 与甲状腺发育不全相关的基因

1.1. 促甲状腺激素受体基因

促甲状腺激素受体(thyroid stimulating hormone receptor, TSHR)是G蛋白偶联受体家族的一种糖蛋白受体, 编码人类TSHR的基因位于14q31, 由10个外显子组成并且编码一段含有764个氨基酸的蛋白质。TSHR基因的功能失活性突变可以导致促甲状腺激素抵抗从而造成先天性甲减, 这是导致先天性甲减最常见的遗传因素。迄今为止已经发现了40余种TSHR基因的功能失活性突变, 而在中国先天性甲减患儿中发现了20种TSHR基因突变(表 1)^[3-10]。我国Fu等^[3]研究显示, 先天性甲减患儿TSHR基因突变的发生率达1.6%, 其中p.R450H突变的发生率尤其高; 台湾地区的研究^[4]也证实大约7%的先天性甲减患儿出现p.R450H突变。

1.

中国地区先天性甲减患儿促甲状腺激素受体基因的突变情况

编号	位置	基因突变		突变类型	甲状腺表现型
编号	位置	DNA	蛋白质	突变类型	甲状腺表现型
注:N示新发现的突变。
1	exon10	c.1582C > T	p.R528C^N	错义突变	发育不良
2	exon4/intron4junction	c.392+4del4N	未知	缺失	发育不良
3	未知	c.1838A > G	p.Y613C^N	错义突变	甲状腺肿大
4	未知	c.326G > A	p.R109Q	错义突变	发育正常
5	未知	c.1576G > A	p.A526T^N	错义突变	发育正常
6	未知	c.2087T > G	p.F696C^N	错义突变	发育正常
7	未知	c.1349G > A	p.R450H	错义突变	发育不良或正常
8	未知	c.1631G > A	p.G544E^N	错义突变	发育正常
9	未知	c.2051C > A	p.A684D^N	错义突变	发育正常
10	未知	c.2272G > A	p.E758K	错义突变	发育正常
11	exon10	c.2066T > G	p.V689G^N	错义突变	甲状腺功能减退或正常
12	exon10	未知	p.D727E	错义突变	发育不良或正常
13	未知	c.G394C	p.G132R^N	错义突变	未知
14	未知	c.T491A	p.M164K^N	错义突变	未知
15	未知	c.A2098G	p.C700E	错义突变	未知
16	未知	c.C1565A	p.A522V	错义突变	未知
17	未知	c.C1582A	p.R528S	错义突变	未知
18	exon1	c.154C > A	p.P52T	错义突变	发育正常
19	exon9	c.733G > A	p.G245S	错义突变	发育正常
20	未知	c.1574T > C	p.F525S	错义突变	未知

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1.2. 配对盒基因8

配对盒基因8(paired box gene, PAX8)属于哺乳动物PAX蛋白家族的一种转录因子。编码人类PAX8的基因位于2q12-q14, 由10个外显子组成。PAX8基因突变会造成甲状腺发育不全^[11]。PAX8基因突变的发生率很低, 并且不同种族和地区也不同, 法国由PAX8基因致病性突变造成先天性甲减的发病率是8.4%^[12], 而捷克的先天性甲减患儿中PAX8基因的突变率只有0.5%^[13]。近年有研究^{[4, 6-7, 14-16]}报道在中国先天性甲减患儿中找到多种PAX8基因突变(表 2)。2015年Fu等^[11]研究发现, 384例中国先天性甲减患儿中有2.38%是由PAX8基因突变导致的。但最新研究^[14]显示中国先天性甲减患儿PAX8基因突变的发生率仅占1.1%。因此, 需要加大样本量对PAX8基因的致病性加以证实。

2.

中国地区先天性甲减患儿PAX8基因突变情况

编号	位置	基因突变		突变类型	甲状腺表现型
编号	位置	DNA	蛋白质	突变类型	甲状腺表现型
注:N示新发现的突变。
1	未知	c.92G > A	p.R31H	错义突变	甲状腺机能缺失或发育不良
2	未知	c.C1064T	p.A355V^N	无义突变	未知
3	未知	c.-26G > A^N	未知	错义突变	未知
4	未知	c.91C > T	p.R31C	错义突变	发育正常
5	未知	c.68G > T^N	p.G23V	错义突变	甲状腺功能减退
6	未知	c.1090C > T^N	p.R364X	错义突变	发育正常
7	未知	c.658C > T^N	p.R220X	错义突变	甲状腺功能减退
8	exon4	c.280G > A	p.D94N^N	错义突变	发育正常
9	exon3	c.122G > T^N	p.G41V	错义突变	发育正常
10	exon3	c.155G/C	p.Arg52Pro	错义突变	发育不良

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1.3. 转录因子基因

甲状腺转录因子在甲状腺发育过程中起着重要的作用, 其中甲状腺转录因子-1(thyroid transcription factor 1, TTF1/NK2 homeobox-1, NKX2.1)是甲状腺前体细胞发育的必需因子, 甲状腺转录因子-2(thyroid transcription factor 2, TTF2/forkhead box E1, FOXE1)可影响甲状腺滤泡细胞前体细胞的迁移^[17]。

NKX2.1是一种包含同源结构域的转录因子, 编码基因位于14q13, 由3个外显子组成。相关研究^[18]发现, 在鼠的胚胎发育过程中NKX2.1表达于甲状腺组织内, 并且NKX2.1在甲状腺滤泡细胞的表达量于甲状腺发育的整个阶段以及成年期都是恒定的。此外, 在分化的甲状腺滤泡细胞中, NKX2.1可以控制甲状腺球蛋白和甲状腺过氧化物酶表达^[19]。迄今为止, 虽然研究人员已经在许多先天性甲减患者中发现了NKX2.1基因突变, 但认为其多属于良性突变, 不参与致病^{[7, 20]}。

FOXE1也是一种包含同源结构域的转录因子, 编码基因位于9q22, 可以编码42 kDa的蛋白质。有报道发现, FOXE1缺失可引起鼠的甲状腺机能缺失或甲状腺异位, 而人类FOXE1基因突变与甲状腺异位之间的关系还没有被证实^[21]。

编码转录因子NKX2.5(the NK2 transcription factor related locus 5)的基因位于5q34, 由两个外显子组成, 编码一段含有324个氨基酸的蛋白质^[2]。NKX2.5表达于甲状腺芽中, 如胚胎中缺乏NKX2.5则甲状腺芽变小, 表明NKX2.5对甲状腺的发育很重要^[22]。最新研究仅发现一种NKX2.5基因突变, 即p.N291I^[7]。

干细胞表达同源盒基因(hematopoietically-expressed homeobox, HHEX)是一种包含同源结构域的转录因子, 在造血干细胞中首次发现。编码HHEX的基因位于人类10号染色体q24, 由4个外显子组成^[23]。研究^[5]显示, HHEX在甲状腺功能中没有发挥作用, 但是在甲状腺发育过程中可以维持NKX2.1、PAX8和FOXE1的表达。对HHEX基因突变的研究甚少, 迄今在中国人先天性甲减的患者中只发现一种HHEX基因突变, 即IVS2+127G/T^[24]。

2. 与甲状腺内分泌障碍相关的基因

2.1. 甲状腺球蛋白基因

甲状腺球蛋白(thyroglobulin, TG)是一种660 kDa的同型二聚体糖蛋白, 在甲状腺组织中的表达量最大。TG既可以作为甲状腺激素合成的基质也可以储存非活性甲状腺激素和碘化物。表达人类TG的基因位于8q24, 由48个外显子组成。甲状腺内分泌障碍发生的主要原因是碘化物有机化缺陷, 而TG储存非活性碘化物, 因此TG基因的突变可以造成甲状腺内分泌障碍发生^[25]。我国已经发现了30余种与先天性甲减有关的TG基因突变(表 3)^{[3, 6, 10, 26-29]}。2016年Hu等^[26]对中国人先天性甲减患者进行大样本TG基因筛查, 发现一种中国人特异性致病性突变—c.274+2T > G, 推测由TG基因突变导致的先天性甲减发生几率为1/101 000。提示TG在先天性甲减的遗传学发病机制中可能起着重要的作用。

3.

中国地区先天性甲减患儿甲状腺球蛋白基因突变情况

编号	位置	基因突变		突变类型	甲状腺表现型
编号	位置	DNA	蛋白质	突变类型	甲状腺表现型
注:N示新发现的突变。
1	未知	IVS3+2T > G	未知	未知	正常
2	exon2	c.3035C > T	p.P1012L	错义突变	未知
3	exon9	c.1382C > T	p.T461IN	错义突变	未知
4	exon26	c.5176C > T	p.L1726FN	错义突变	未知
5	exon15	c.3332C > G	p.T1111RN	错义突变	未知
6	未知	c.2281C > T	p.P761S	错义突变	未知
7	未知	c.4493C > T	p.T1498M	错义突变	未知
8	未知	c.4859C > T	p.T1620M	错义突变	未知
9	exon44	c.7753C > T	p.R2585W	错义突变	未知
10	exon2	c.103G > A	p.R38K	错义突变	未知
11	exon3	c.262C > T	p.R88W	错义突变	未知
12	intron3	c.274+2T > G	未知	剪接供体位点	未知
13	exon8	c.925A > G	p.T309A	错义突变	未知
14	exon10	c.2222C > T	p.T741M	错义突变	未知
15	exon17	c.3808C > T	p.R1270C	错义突变	未知
16	exon22	c.4575G > T	p.Q1525H	错义突变	未知
17	exon22	c.4604A > G	p.D1535G	错义突变	未知
18	exon27	c.5318C > A	p.A1773D	错义突变	未知
19	exon31	c.5711T > G	p.C1904G	错义突变	未知
20	exon31	c.5791A > G	p.I1931V	错义突变	未知
21	exon7	c.799C > T	p.L267F^N	错义突变	未知
22	exon13	c.3153T > A	p.C1051X^N	错义突变	未知
23	exon36	c.6391delTTGT	p.L2131fsX2152^N	框移突变	未知
24	intron39	c.6782+1delG	未知	剪接供体位点	未知
25	exon47	c.8119C > T	p.R2707X	无义突变	甲状腺功能减退
26	exon31	c.5766C > A	p.Y1922X^N	无义突变	正常
27	exon10	c.G2687A	p.R877Q^N	错义突变	正常
28	exon40	c.C7006T	p.R2317X	无义突变	正常
29	exon9	c.1348delT^N	未知	框移突变	正常
30	exon9	c.1351C > T^N	p.R432X	错义突变	甲状腺肿大
31	intron3	g.IVS3+2T > G^N	未知	剪接供体位点	正常
32	exon9	c.1712delT^N	未知	框移突变	甲状腺肿大
33	exon27	c.5350C > T^N	p.Q1765X	错义突变	正常
34	exon33	c.6047delA^N	p.E1997R	框移突变	正常

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2.2. 甲状腺过氧化物酶基因

甲状腺过氧化酶(thyroid peroxidase, TPO)是一种甲状腺特异性的亚铁血红素过氧化物酶, 位于甲状腺细胞的顶端, 在甲状腺激素合成过程中起着重要作用。编码人类TPO的基因位于2p25, 由17个外显子组成。研究^[30]显示, TPO基因突变可能是引起先天性甲减最常见的原因, 而大多数甲状腺内分泌障碍的患者都是由于TPO基因突变造成的。TPO基因突变在亚洲被广泛研究, 我国已发现多种与先天性甲减有关的TPO基因突变(表 4)^{[6, 10, 29, 31-37]}。2015年Fu等^[31]对中国人先天性甲减患者进行TPO基因筛查, 发现1%的先天性甲减是由TPO基因的致病性突变导致。另有研究^[32]显示, 2268 insT是中国大陆地区和中国台湾地区先天性甲减患儿TPO基因最常发生的突变。

4.

中国地区先天性甲减患儿甲状腺过氧化酶基因突变情况

编号	位置	基因突变		突变类型	甲状腺表现型
编号	位置	DNA	蛋白质	突变类型	甲状腺表现型
注:N示新发现的突变。
1	未知	c.664G > T	p.D222Y	错义突变	未知
2	未知	c.1327G > C	p.A443P^N	错义突变	未知
3	未知	c.1471C > T	p.R491C^N	错义突变	未知
4	exon11	c.1970T > C^N	p.I657T	错义突变	甲状腺肿大
5	exon16	c.2665G > T^N	p.G889X	错义突变	甲状腺肿大
6	exon13	c.2266T > C	p.C765R	错义突变	甲状腺肿大
7	exon7	c.670-672del^N	p.D224del	缺失	甲状腺肿大或正常
8	exon13	c.2268dupT	p.E757K	未知	甲状腺肿大或结节性甲状腺肿
9	exon16	c.2647C > T	p.P883S	错义突变	甲状腺肿大或正常
10	未知	未知	p.R648Q	错义突变	甲状腺肿大
11	exon10	c.1682C > T	p.T561M^N	错义突变	甲状腺肿大
12	exon14	c.2422delT	p.C808AfsX24	框移突变	甲状腺肿大
13	未知	c.2395G > A	p.E799K	错义突变	未知
14	未知	c.1784G > C	p.R595T	错义突变	未知
15	exon13	c.2268 insT^N	p.Glu757X	未知	甲状腺肿大
16	exon13	c.2243del T^N	未知	框移突变	未知
17	exon3	c.G157CN	p.A53P	错义突变	未知
18	exon8	c.843delC^N	未知	框移突变	正常
19	exon14	c.2413delC^N	未知	框移突变	甲状腺肿大
20	exon9	未知	p.G493S^N	错义突变	正常
21	exon13	未知	p.D796Y^N	错义突变	正常
22	exon13	c.2268–2269insTN	未知	框移突变	正常
23	exon8	c.1207G > T	p.A373S	错义突变	甲状腺肿大
24	exon8	c.1283 G > C	p.S398T	错义突变	甲状腺肿大
25	exon11	c.2088 C > T	p.D666D	错义突变	正常
26	exon11	c.2089 G > A	未知	未知	甲状腺肿大
27	exon8	c.1186C > T^N	p.Arg396Cys	错义突变	正常

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2.3. 甲状腺氧化酶2基因

碘化物的氧化和有机化需要TPO的作用以及作为最终电子受体的H₂O₂, 因此在甲状腺激素合成过程中H₂O₂起着重要的作用。研究显示, 在甲状腺产H₂O₂的系统中甲状腺氧化酶2(thyroid oxidase 2, THOX2/dual oxidase 2, DUOX2)是一个重要的组成成分, DUOX2可能是维持正常甲状腺功能最关键的酶^[38]。DUOX2基因突变会导致甲状腺内分泌障碍, 从而引起先天性甲减的发生。编码人类DUOX2的基因位于15q15.3, 由33个外显子组成。迄今为止, 包括我国在内的许多国家对DUOX2基因与先天性甲减的关系进行了大量研究, 在DUOX2基因发现的突变也是最多的(表 5)^{[3, 6, 10, 27, 31, 33, 39-44]}。2015年Fu等^[39]对中国人先天性甲减患者的DUOX2基因进行大样本筛查, 发现突变率可以达到29%。还有研究显示DUOX2基因的突变与短暂性甲减也有着密切的联系^[27]。

5.

中国地区先天性甲减患儿甲状腺氧化酶2基因突变情况

编号	位置	基因突变		突变类型	甲状腺表现型
编号	位置	DNA	蛋白质	突变类型	甲状腺表现型
注:N示新发现的突变。
1	未知	c.1588A > T	p.K530X	错义突变	正常或甲状腺功能减退或甲状腺肿大
2	未知	c.2635G > A	p.E879K	错义突变	正常或甲状腺肿大
3	未知	c.3339delC	未知	缺失	未知
4	未知	c.1232G > A	p.R411K	错义突变	未知
5	未知	c.3329G > A	p.R1110Q	错义突变	正常或甲状腺功能减退或甲状腺肿大
6	未知	c.2048G > T^N	p.R683L	错义突变	正常或甲状腺肿大
7	未知	c.4027G > T	p.L1343F	错义突变	正常或甲状腺肿大
8	未知	c.3413C > A^N	p.A1138D	错义突变	正常或甲状腺肿大
9	未知	c.2524C > T	p.R842X	错义突变	正常
10	未知	c.184C > T	p.P62S	错义突变	未知
11	未知	c.1931A > G	p.K644RT/B	未知	未知
12	未知	c.2335G > A	p.V779M	错义突变	未知
13	未知	c.2894C > T	p.S965L	错义突变	未知
14	未知	c.4408C > T	p.R1470W	错义突变	未知
15	未知	c.3896+1G > T	未知	剪接突变	未知
16	未知	c.2654G > T	p.R885L	错义突变	甲状腺肿大
17	未知	c.2102-2104delGAG	p.G702del^N	框内缺失	正常或甲状腺肿大
18	未知	c.3478-3480delCTG	p.L1160del^N	框内缺失	正常
19	未知	c.3251G > A	p.R1084QN	错义突变	正常
20	未知	c.3967G > A	p.A1323TN	错义突变	正常
21	未知	c.4475G > A	p.R1492H^N	错义突变	甲状腺功能减退
22	未知	c.3391G > T	p.A1131SN	错义突变	正常或甲状腺肿大
23	未知	c.244C > A	p.R82S^N	错义突变	甲状腺肿大
24	未知	c.3340delC^N	p.L1114SfsX56	框移突变	正常或甲状腺功能减退或甲状腺肿大
25	未知	c.903G > T^N	p.W301C	错义突变	正常或甲状腺功能减退
26	未知	c.1736T > C^N	p.L579P	错义突变	正常
27	未知	c.4000C > T	p.R1334W^N	错义突变	正常或甲状腺肿大
28	未知	c.605-621del17	未知	缺失	甲状腺肿大
29	exon20	c.554+5C > T	p.R885Q	错义突变	正常或甲状腺肿大
30	未知	未知	p.W734X^N	无义突变	甲状腺肿大
31	未知	未知	p.R701X	错义突变	甲状腺肿大
32	未知	未知	p.W1181G^N	错义突变	甲状腺肿大
33	未知	未知	p.S660L^N	错义突变	甲状腺肿大
34	未知	未知	p.A1206T^N	错义突变	甲状腺肿大
35	未知	未知	p.N100D^N	错义突变	甲状腺肿大
36	未知	未知	p.R1267W^N	错义突变	甲状腺肿大
37	exon28	c.G3632A	p.R1211H	错义突变	甲状腺肿大
38	exon17	c.T2033C	p.H678R	错义突变	甲状腺肿大
39	exon10	c.1060C > T	p.R354^N	错义突变	甲状腺肿大
40	exon28	c.3616G > A	p.A1206T	错义突变	甲状腺肿大
41	exon10	c.C1329T	p.R376W	错义突变	甲状腺肿大

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2.4. 甲状腺氧化酶成熟因子2

甲状腺氧化酶成熟因子2(dual-oxidase maturation factor 2, DUOXA2)基因与DUOX2基因共表达, 它是DUOX同工酶的成熟因子, 在DUOX2的成熟和活化过程中起着重要作用。编码人类DUOXA2的基因位于15号染色体, 由6个外显子组成。Liu等^[45]研究表明, DUOXA2基因发生突变会造成甲状腺H₂O₂的产生能力丧失, 从而导致先天性甲减的发生。我国仅在几例先天性甲减患者中发现有DUOXA2基因突变, 包括c.C738G, c.554+5C > T和c.C78G突变^{[33, 41, 45-46]}, 后两者是新发现的基因突变。

2.5. SLA26A4基因

SLA26A4基因属于多功能性SLA26转运体家族的一员, 它可以促进碘化物从甲状腺细胞膜的顶端到滤泡腔的流动。我国学者对中国人先天性甲减患儿的SLA26A4基因进行筛查, 发现了6种突变, 包括c.1143-2A > G、p.V233L、p.P469S、p.M147I、p.V609G及p.D661E, 其中p.P469S是新发现的基因突变^{[6, 10, 47]}。SLA26A4基因与先天性甲减之间的关系发病的影响尚不明确, 需要更大样本加以证明。

此外, 影响甲状腺激素合成还有碘化钠同向转运体(Na⁺/Ⅰ-symporter, NIS)。通过克隆NIS(公认的基因标志是SLC5A5)基因发现, SLC5A5基因突变为先天性碘化物转运缺陷的原因之一。虽然国际上已经发现了10余种SLC5A5基因突变, 但中国的研究人员尚未在先天性甲减患儿中发现该基因的突变。

3. 总结与展望

综上, 先天性甲减的发病机制尚不明确, 主要为甲状腺发育不全和甲状腺内分泌障碍所致, 中枢性先天性甲减和甲状腺或靶器官反应低下也是先天性甲减的发病原因。目前主要针对前两种发病机制进行相关基因的研究, 如TSHR、PAX8、TG、TPO及DUOX2等基因, 以DUOX2基因的研究最多, 在这些基因发现的众多突变位点为先天性甲减致病机制的研究提供了依据。但NKX2.1、FOXE1、NKX2.5、HHEX、DUOXA2、SLA26A4及NIS等基因突变所致先天性甲减的发生率极低, 研究尚不深入。而且国际上已经发现了多种与先天性甲减发病相关的候选基因, 需要筛选出中国人先天性甲减的基因谱, 还需要验证候选基因突变与先天性甲减之间的关系。最后, 应致力于筛查发生率较高的基因突变并通过功能实验加以验证, 为先天性甲减的临床诊治提供有力依据。

Biography

陈晓宇, 女, 硕士研究生

CHEN Xiao-Yu,Email:957509010@qq.com

Contributor Information

陈晓宇 (Xiao-Yu CHEN), Email: 957509010@qq.com.

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[b1] 1.Chiesa Al, Prieto L, Mendez V, et al. Prevalence and etiology of congenital hypothyroidism detected through an argentine neonatal screening program(1997-2010) Horm Res Paediatr. 2013;80(3):185–192. doi: 10.1159/000354409. [DOI] [PubMed] [Google Scholar]

[b2] 2.Nettore IC, Cacace V, De Fusco C, et al. The molecular causes of thyroid dysgenesis:a systematic review. https://link.springer.com/article/10.3275/8973. J Endocrinol Invest. 2013;36(8):654–664. doi: 10.3275/8973. [DOI] [PubMed] [Google Scholar]

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中国儿童先天性甲状腺功能减退症的基因学研究进展

Advances in genetic research of congenital hypothyroidism in China

Abstract

Abstract

1. 与甲状腺发育不全相关的基因

1.1. 促甲状腺激素受体基因

1.

1.2. 配对盒基因8

2.

1.3. 转录因子基因

2. 与甲状腺内分泌障碍相关的基因

2.1. 甲状腺球蛋白基因

3.

2.2. 甲状腺过氧化物酶基因

4.

2.3. 甲状腺氧化酶2基因

5.

2.4. 甲状腺氧化酶成熟因子2

2.5. SLA26A4基因

3. 总结与展望

Biography

Contributor Information

References

ACTIONS

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RESOURCES

Cite

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PERMALINK

中国儿童先天性甲状腺功能减退症的基因学研究进展

Advances in genetic research of congenital hypothyroidism in China

Abstract

Abstract

1. 与甲状腺发育不全相关的基因

1.1. 促甲状腺激素受体基因

1.

1.2. 配对盒基因8

2.

1.3. 转录因子基因

2. 与甲状腺内分泌障碍相关的基因

2.1. 甲状腺球蛋白基因

3.

2.2. 甲状腺过氧化物酶基因

4.

2.3. 甲状腺氧化酶2基因

5.

2.4. 甲状腺氧化酶成熟因子2

2.5. SLA26A4基因

3. 总结与展望

Biography

Contributor Information

References

ACTIONS

PERMALINK

RESOURCES

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