Genetic and Phenotypic Characteristics of Congenital Hypothyroidism in a Chinese Cohort.
Genetic and Phenotypic Characteristics of Congenital Hypothyroidism in a Chinese Cohort.
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中国人群先天性甲状腺功能减退症的遗传和表型特征
DOI：
10.3389/fendo.2021.705773
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发表时间：
2021
影响因子：
5.2
通讯作者：
Xue P
中科院分区：
文献类型：
--
作者：
Long W;Guo F;Yao R;Wang Y;Wang H;Yu B;Xue P
先天性甲状腺功能减退症（CH）的分子病因和基因型-表型相关性尚不清楚。我们使用全外显子组测序对42例新生儿CH进行了遗传分析。根据受影响基因的数量将患者分为单基因组和多基因组，或根据检测到的变异模式将患者分为单等位基因组、双等位基因组和少基因组。比较两组患者的临床特点。甲状腺发育不良（TD） 10例，甲状腺肿大5例，而正常大小腺体原位（GIS） 27例。我们在29例患者中鉴定出5个基因的58个变异。最常见的变异基因是DUOX2(70.7%)，其次是TSHR（12.1%）、DUOXA2（10.3%）和TPO（5.2%）。引起激素生成障碍（DH）的基因变异比引起TD的基因变异更常见（87.9%比12.1%）。检测到变异的患者中，单基因变异26例（89.7%），其中双等位变异22例（双等位组），单等位变异4例（单等位组）。3例（10.3%）患者携带2个或3个基因变异（多基因组或少基因组）。多基因组1岁时左旋甲状腺素（L-T4）剂量高于单基因组（p = 0.018）。单等位基因组25%的患者和双等位基因组59.1%的患者L-T4剂量可控减少；然而，在低原组中没有观察到L-T4剂量减少的患者。正常大小的GIS患者占我们队列的大多数。致DH基因的遗传缺陷比致TD基因的遗传缺陷更为常见，以DUOX2的双等位基因变异为主。DH可能是中国人CH的主要病理生理机制。
The molecular etiology and the genotype–phenotype correlation of congenital hypothyroidism (CH) remain unclear. We performed genetic analysis in 42 newborns with CH using whole-exome sequencing. Patients were divided into a single-gene group and a multi-gene group according to the number of affected genes, or divided into a monoallelic group, a biallelic group, and an oligogenic group according to the pattern of the detected variants. The clinical characteristics were compared between groups. Thyroid dysgenesis (TD) was observed in 10 patients and goiter in 5 patients, whereas 27 patients had normal-sized gland-in-situ (GIS). We identified 58 variants in five genes in 29 patients. The genes with the most frequent variants were DUOX2 (70.7%), followed by TSHR (12.1%), DUOXA2 (10.3%), and TPO (5.2%). Variants in the genes causing dyshormonogenesis (DH) were more common than those in the genes causing TD (87.9% versus 12.1%). Among the patients with detected variants, 26 (89.7%) were harboring a single gene variant (single-gene group), which include 22 patients harboring biallelic variants (biallelic group) and four patients harboring monoallelic variants (monoallelic group). Three (10.3%) patients harbored variants in two or three genes (multi-gene group or oligogenic group). Compared with the single-gene group, the levothyroxine (L-T4) dose at 1 year of age was higher in the multi-gene group (p = 0.018). A controllable reduction in the L-T4 dose was observed in 25% of patients in the monoallelic group and 59.1% of patients in the biallelic group; however, no patients with such reduction in the L-T4 dose were observed in the oligogenic group. Patients with normal-sized GIS accounted for the majority of our cohort. Genetic defects in the genes causing DH were more common than those in the genes causing TD, with biallelic variants in DUOX2 being dominant. DH might be the leading pathophysiology of CH in Chinese individuals.
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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：
10.1016/j.beem.2018.05.002
发表时间：
2018-08-01
影响因子：
7.4
作者：
Persani, Luca;Rurale, Giuditta;Fugazzola, Laura
通讯作者：
Fugazzola, Laura
用原位腺体甲状腺功能减退症中八个已知的病因基因的全面筛查。
DOI：
10.1210/jc.2016-1879
发表时间：
2016-12
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Nicholas AK;Serra EG;Cangul H;Alyaarubi S;Ullah I;Schoenmakers E;Deeb A;Habeb AM;Almaghamsi M;Peters C;Nathwani N;Aycan Z;Saglam H;Bober E;Dattani M;Shenoy S;Murray PG;Babiker A;Willemsen R;Thankamony A;Lyons G;Irwin R;Padidela R;Tharian K;Davies JH;Puthi V;Park SM;Massoud AF;Gregory JW;Albanese A;Pease-Gevers E;Martin H;Brugger K;Maher ER;Chatterjee VK;Anderson CA;Schoenmakers N
通讯作者：
Schoenmakers N
影响因子：
2.9
作者：
Sorapipatcharoen K;Tim-Aroon T;Mahachoklertwattana P;Chantratita W;Iemwimangsa N;Sensorn I;Panthan B;Jiaranai P;Noojarern S;Khlairit P;Pongratanakul S;Suprasongsin C;Korwutthikulrangsri M;Sriphrapradang C;Poomthavorn P
通讯作者：
Poomthavorn P
暂时性和永久性先天性甲状腺功能减退症基因突变与表型特征之间的复杂关系：汇总文献数据分析
影响因子：
2.8
作者：
Long, Wei;Zhou, Lingna;Yu, Bin
通讯作者：
Yu, Bin