Molecular and clinical genetics of the transcription factor GLIS3 in Chinese congenital hypothyroidism
Molecular and clinical genetics of the transcription factor GLIS3 in Chinese congenital hypothyroidism
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中国先天性甲状腺功能减退症转录因子GLIS3的分子和临床遗传学
DOI：
10.1016/j.mce.2021.111223
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发表时间：
2021-03
影响因子：
4.1
通讯作者：
Huai-Dong Song
中科院分区：
文献类型：
--
作者：
Rui-Jia Zhang;Jun-Xiu Zhang;Wen-Hua Du;Feng Sun;Ya Fang;Cao-Xu Zhang;Zheng Wang;Feng-Yao Wu;Bing Han;Wei Liu;Shuang-Xia Zhao;Jun Liang;Huai-Dong Song
转录因子GLIS 3是激素生物合成和甲状腺发育的重要因子，GLIS 3的突变相对罕见。在大多数甲状腺外异常和先天性甲状腺功能减退症（CH）患者中，GLIS 3的11个外显子中有一个以上缺失，仅报道了18种与甲状腺疾病相关的GLIS 3错义变体。本研究的目的是报告携带GLIS 3变体的CH患者的家族史和分子基础。招募了353名患有CH的非血缘婴儿，并对其进行CH相关基因的靶向外显子组测序。在体外对GLIS 3基因的转录活性和细胞定位进行了研究。我们在19例CH患者中发现了20个异源性GLIS 3外显子错义变异，其中包括8个新位点。1例患者携带复合异源性GLIS 3变异（p.His34Arg和p.Pro835Leu）。所有变异体均不影响核定位。然而，位于GLIS 3蛋白N-末端和C-末端区域的三个变体（p.His34Arg、p.Pro835Leu和p.Ser893Phe）下调了甲状腺激素（TH）生物合成所需的几个基因的转录激活。这项对CH患者的研究扩展了目前对GLIS 3变异体谱及其导致TH生物合成缺陷的机制的认识。
The transcription factor GLIS3 is an important factor in hormone biosynthesis and thyroid development, and mutations inGLIS3are relatively rare. Deletions of more than one of the 11 exons ofGLIS3occur in most patients with various extrathyroidal abnormalities and congenital hypothyroidism (CH), and only 18 missense variants ofGLIS3related to thyroid disease have been reported. The aim of this study was to report the family history and molecular basis of patients with CH who carryGLIS3variants. Three hundred and fifty-three non-consanguineous infants with CH were recruited and subjected to targeted exome sequencing of CH-related genes. The transcriptional activity and cellular localization of the variants inGLIS3were investigatedin vitro. We identified 20 heterozygousGLIS3exonic missense variants, including eight novel sites, in 19 patients with CH. One patient carried compound heterozygousGLIS3variants (p.His34Arg and p.Pro835Leu). None of the variants affected the nuclear localization. However, three variants (p.His34Arg, p.Pro835Leu, and p.Ser893Phe) located in the N-terminal and C-terminal regions of the GLIS3 protein downregulated the transcriptional activation of several genes required for thyroid hormone (TH) biosynthesis. This study of patients with CH extends the current knowledge surrounding the spectrum ofGLIS3variants and the mechanisms by which they cause TH biosynthesis defects.
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影响因子：
14.9
作者：
Beak, Ju Youn;Kang, Hong Soon;Kim, Yong-Sik;Jetten, Anton M.
通讯作者：
Jetten, Anton M.
综合筛选21个候选基因分析中国先天性甲状腺功能减退症的遗传特征
影响因子：
5.8
作者：
Sun F;Zhang JX;Yang CY;Gao GQ;Zhu WB;Han B;Zhang LL;Wan YY;Ye XP;Ma YR;Zhang MM;Yang L;Zhang QY;Liu W;Guo CC;Chen G;Zhao SX;Song KY;Song HD
通讯作者：
Song HD
DOI：
10.1210/jc.2015-1827
发表时间：
2015-10
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Dimitri P;Habeb AM;Gurbuz F;Millward A;Wallis S;Moussa K;Akcay T;Taha D;Hogue J;Slavotinek A;Wales JK;Shetty A;Hawkes D;Hattersley AT;Ellard S;De Franco E
通讯作者：
De Franco E
影响因子：
3.7
作者：
Szczepanek-Parulska E;Budny B;Borowczyk M;Zawadzka K;Sztromwasser P;Ruchała M
通讯作者：
Ruchała M
影响因子：
2.7
作者：
Alghamdi KA;Alsaedi AB;Aljasser A;Altawil A;Kamal NM
通讯作者：
Kamal NM