Nodal基因与先天性甲状腺功能低下症

<正>先天性甲状腺功能低下症(Congonital hypothyrowidism,CH,先天性甲减,也称呆小病或克汀病),是指在胎儿期或出生2个月内发生的甲减。CH分为三大类:1)原发性甲减,是指甲状腺自身发育不全、发育不良、甲状腺激素(TH)合成和转运过程等致TH不足而引起[1];2)中枢性甲减,是由于下丘脑或垂体对甲状腺激素水平调节缺陷所致,TRHR基因、TRH基因突变等;3)周围性甲减,受体病或受     

母体甲状腺素传递给患完全性碘有机化功能缺陷的先天性甲减胎儿

大多数先天性甲减患儿在出生时常无甲减表现,出生后数周才有表现;而母体患甲减时,在妊娠早期即影响胎儿的神经系统发育。母体的甲状腺激素能否传递给胎儿,是一个需阐明的重要问题。 作者从1981年起给荷兰全国的新生儿作了甲状腺功能普查,共发现23例患完全性碘有机化缺陷的先天性甲减患儿,检出率为1:6万,占全部检出的先天性甲减的5％,同时还诊断了15例先天性甲状腺未发育患儿。 先天性完全性碘有机化缺陷的诊断标准如下:1,出生时新生儿血清甲状腺素(T_4)浓度为35～     

先天性甲状腺功能减退症患儿的诊治

先天性甲状腺功能减退症(congenital hypothyroidism,CH)简称先天性甲减,是指因甲状腺激素产生不足或其受体缺陷所导致的先天性疾病.原发性先天性甲减是临床上最常见的一类先天性甲减.临床经验表明,在出生后几周内给予甲状腺激素替代治疗,可以预防或明显减轻先天性甲减导致的神经精神发育异常.因此,必须建立...     

甲状腺激素合成障碍与先天性甲状腺功能低下症

<正>甲状腺激素(TH)是机体生命活动的重要激素,承担着机体产热、物质代谢、各器官组织的功能,特别是脑的功能、促进生长发育等重要职责。TH即指甲状腺素(T_4)、三碘甲状腺原氨酸(T_3)。先天性甲状腺功能低下症(先天性甲减,CH)主要由先天性甲状腺发育缺陷或TH合成缺陷,而致TH不足。一个完善的TH合成,大致需经历下述各     

Titf1/NKx2.1基因与先天性甲状腺功能低下症

正先天性甲状腺功能低下症(Congenital hypothyroidism,CH,简称先天性甲减)是婴幼儿最常见的内分泌疾病[1]。主要表现为甲状腺激素(TH)分泌不足或完全缺乏,导致甲状腺功能低下,生长发育落后和智力发育迟缓,先天性甲减80%～85%系因甲状腺发育缺陷[2],约15%～20%为甲状     

先天性甲状腺功能减退症的基因基础研究进展

先天性甲状腺功能减退症(CH)是小儿常见的内分泌疾病,已经明确,影响甲状腺发生、发育的因素如甲状腺转录因子(TTF)-1、TTF-2、Pax-8的基因异常会导致甲状腺组织发育不良;而在甲状腺激素合成过程中的缺陷,如促甲状腺激素受体、甲状腺球蛋白、钠-碘同向转运体基因突变及碘活化过程障碍可以导致有正常甲状腺组织的甲状腺功能减退症;其他,如促甲状腺激素β基因引起下丘脑和垂体功能的异常及甲状腺激素抵抗综合征也在CH发病中起重要作用.     

DUOXA2基因与先天性甲状腺功能低下症

<正>过氧化氢产生系统,在碘的氧化、有机化、甲状腺激素合成过程中发挥着不可缺少的作用。流行病学资料,约20%先天性甲状腺功能减退症(congenital hypothyroidism,CH,先天性甲减)是因甲状腺激素(TH)合成障碍所致。其中第一步即碘的氧化,其中许多基因参与着碘的氧化过程;甲状腺过氧化物酶(TPO)基因~([1])、二元氧化酶2(DUOX2)基因~([2])、二元氧化酶成熟因子2(DUOXA2)基因~([3])等。     

先天性甲状腺功能减退症的基因基础研究进展

先天性甲状腺功能减退症(CH)是小儿常见的内分泌疾病，已经明确，影响甲状腺发生、发育的因素如甲状腺转录因子(TTF)-1、TTF-2、Pax-8的基因异常会导致甲状腺组织发育不良；而在甲状腺激素合成过程中的缺陷，如促甲状腺激素受体、甲状腺球蛋白、钠-碘同向转运体基因突变及碘活化过程障碍可以导致有正常甲状腺组织的甲状腺功能减退症；其他，如促甲状腺激素β基因引起下丘脑和垂体功能的异常及甲状腺激素抵抗综合征也在CH发病中起重要作用。     

TSH受体基因与先天性甲状腺功能低下症

<正>促甲状腺激素受体(TSHR)失活性突变,可导致甲状腺先天性发育不良和先天性甲状腺功能低下症(先天性甲减,CH)。准确地说TSH是由腺垂体分泌的激素,主要负责调节甲状腺细胞的分化、增殖、甲状腺的血液供应以及甲状腺激素的合成和分泌,在维持正常甲状腺发育和功能中起重要的调节作用。是内分泌糖蛋白激素家族成员(包括LH、     

TG基因突变与先天性甲状腺功能低下症

<正>先天性甲状腺功能低下症(congonital hypothy roidism,CH,先天性甲减),至2005年报道新生儿发生率约为1/3000～4000~([1])。近年来研究,大致85%～90%的病人由甲状腺发育不全引起,10%～15%是因甲状腺激素(TH),合成障碍或碘的有机化障碍,致TH合成不足而引发CH。特别是相应的易感基因突变~([2]),调控着甲状腺的发育及TH的合成。如甲状腺球蛋白基因。     

DUOXS defects: Genotype-phenotype correlations

Congenital hypothyroidism (CH) is the most common congenital endocrine disorder, accounting for up to 1:1500 newborns per year. CH can be related to defects in either formation and migration of the thyroid gland (dysgenesis) or thyroid hormone synthesis. The pathogenesis of dysgenetic CH is still largely unknown. On the contrary, several mutations have been found in different genes involved in thyroid dyshormonogenesis (such as pendrin, thyroperoxidase-TPO, thyroglobulin). Recently, new genes involved in the etiology of dyshormonogenesis have been identified: dual oxidase 2 (DUOX2) and dual oxidase maturation factor 2 (DUOXA2). They are the principal elements generating the hydrogen peroxide needed for TPO function. Mutations in these genes have been associated to transient or permanent CH, with a high intra and interfamilial phenotypic variability. Some hypotheses have been drawn to explain the variability of the DUOX2/A2 phenotype. Among them, the existence of other H₂0₂ generating systems, the different requirements for thyroid hormones according to age, the ethnicity, the intake of iodine. In the present paper, the genetic and clinical features of CH caused by defects in the peroxide generator system will be revised.     

Congenital hypothyroidism caused by new mutations in the thyroid oxidase 2 (THOX2) gene

OBJECTIVE: Congenital primary hypothyroidism (CH) occurs in one of 4000 births and in 20% of the cases CH is due to a defect in thyroid hormonogenesis. Candidate genes were examined to determine the precise aetiology of suspected dyshormonogenesis in CH. DESIGN: The genes that code for thyroid peroxidase (TPO), pendrin (PDS), sodium iodide symporter (NIS) and thyroid oxidase 2 (THOX2) were sequenced directly from genomic DNA. PATIENTS: Two girls found to have CH in the neonatal screening programme and suspected of having thyroid dyshormonogenesis were investigated to identify their molecular defect. RESULTS: Patient A had a novel heterozygous 1 bp insertion in the THOX2 gene (ins602g). This insertion results in a frameshift that predicts a premature stop at codon 300. Analysis of cDNA, transcribed from lymphocyte RNA, showed that this mutation causes skipping of exon 5, resulting in a frameshift and a premature stop at codon 254. The euthyroid mother was also a heterozygous carrier of the mutation whereas the father was homozygous for the wild-type THOX2 gene. In patient B, compound heterozygous mutations (ins602g-->fsX300 and D506N) were identified. D506N was present in one allele of the clinically unaffected mother and in a brother, whereas the euthyroid father was heterozygous for ins602g. Sixty normal individuals did not harbour the mutations. Sequencing of the TPO, PDS and NIS genes revealed no mutations. CONCLUSIONS: The identified THOX2 mutations, which have not been described previously, are the probable causes of CH in the patients. Mutations in the THOX2 gene should be considered as the molecular cause of CH in young patients with thyroid dyshormonogenesis.     

High prevalence of thyroid peroxidase gene mutations in patients with thyroid dyshormonogenesis

OBJECTIVE: Thyroid dyshormonogenesis is a genetically heterogeneous group of inherited disorders in the enzymatic cascade of thyroid hormone synthesis that result in congenital hypothyroidism (CH). Thyroid peroxidase gene (TPO) mutations are one of the most common causes of thyroid dyshormonogenesis. The aim of this study was to identify TPO gene defects in a cohort of patients with thyroid dyshormonogenesis from Slovenia, Bosnia, and Slovakia. DESIGN AND METHODS: Forty-three patients with permanent CH and orthoptic thyroid glands from 39 unrelated families participated in the study. Mutational analysis of the TPO gene and part of its promoter consisted of single-stranded conformation polymorphism analysis, sequencing, and restriction fragment length polymorphism (RFLP) analysis. Results: TPO gene mutations were identified in 46% of participants. Seven different mutations were identified, four mutations of these being novel, namely 613C > T (R175X), 1519_1539del (A477_N483del), 2089G > A (G667S), and 2669G > A (G860R). Only a single allele mutation was identified in 65% of the TPO mutation carriers. CONCLUSIONS: The results showed a higher prevalence of TPO gene mutations in thyroid dyshormonogenesis when compared with published studies. The high percentage of single allele mutations implied possible intronic or regulatory TPO gene mutations or monoallelic expression.