一家两例先天性甲状腺功能低下报告

患儿男,16天,汉族,因皮肤黄染14天、哭声弱、哺乳差伴便秘10天入院。查体:一般情况好,前囟3.5cm×3.5 cm,后囟1.0cm×1.0cm,颅骨骨缝未对合,全身皮肤黄染。患儿系二胎二产,自然分娩,出生体重3.8 kg,出生3天查甲状腺功能,T3 0.3 nmol/L,T4 2.7nmol,L,     

一家两例先天性甲状腺功能低下报告

患儿男,16天,汉族,因皮肤黄染14天、哭声弱、哺乳差伴便秘10天入院.查体:一般情况好,前囟3.5cm×3 .5cm,后囟1.0cm×1.0cm,颅骨骨缝未对合,全身皮肤黄染.     

先天性甲状腺功能减退症致病基因研究进展

先天性甲状腺功能减退症(CH)是由于甲状腺激素合成不足所造成的一种遗传代谢性疾病,现已证实有众多基因的突变与其发病有关。该文就已定位克隆的CH致病基因结构、功能和突变作一综述,以加深对CH致病基因研究进展的了解。     

先天性甲状腺功能减退症相关致病基因研究进展

先天性甲状腺功能减退症(CH)是指在某些病因的作用下,胚胎期下丘脑-垂体-甲状腺轴的发生、发育和功能代谢出现异常,导致患儿血循环中甲状腺激素水平下降,如未得到及时诊断与治疗,患儿的生长发育会受到严重影响。近年来,基因检测逐步应用于临床,致病基因的发现将有利于CH的早期诊断或症状前诊断,以及产前诊断。文章从导致CH的综合征和非综合征两方面阐述相关基因突变的研究进展。     

甲状腺球蛋白增高的先天性甲状腺功能减退症1例报告并文献复习

目的 探讨甲状腺球蛋白(TG)增高的先天性甲状腺功能减退症(CH)家系的临床特征及TG基因变异特征.方法 回顾分析1个TG增高的CH家系的临床及TG基因检测结果,并复习相关国内外文献.结果 先证者,女,45日龄,生后黄疸消褪延迟伴便秘.甲状腺功能检测提示为CH,同时发现TG水平增高.基因检测结果显示患儿TG基因存在c....     

先天性甲状腺功能低下的新生儿筛查

用新生儿生后30分钟内采的脐血和生后4～7天的末梢血分别用放免法测TSH和T_4来判断甲状腺功能。共筛查32999例新生儿,查出先天性甲低3例和1例低T_4血症。先天性甲低患者用干甲状腺片治疗,随访观察效果较好。本文对筛查方法、目的和意义进行了讨论。     

先天性甲状腺功能减退症3例误诊分析

先天性甲状腺功能减退症(简称甲低)如能早期诊治,可避免不可逆的智力障碍。本文3例,因多次误诊而延误治疗,现报告如下。例1,男,8月。因食少,皮肤干燥,便秘8个月入院。G_4P_4,足月顺产,出生体重3.75kg。生后即食少,少哭多睡,每隔4～5天排1次大便,大便干结、量中。无吐泻。皮肤黄疸至3个月才完全消退,多     

先天性甲状腺功能低下16例误诊分析

目的为提高对先天性甲状腺功能低下症（congenital hypothyroidism，CH）的临床认识，减少误诊和漏诊，故分析此病的误诊原因。方法对1994—2005年诊断CH的16例病例资料回顾性分析其病因、临床症状、体征和实验室检查。结果发现CH临床初次误诊率高达73％，多被误诊为：婴儿肝炎综合征、贫血、佝偻病、先天性巨结肠等疾病。结论CH临床表现无特异性，但CH并非罕见，临床误诊率高，需提高对本病的认识，以降低误诊率。     

小儿先天性甲状腺功能减退症46例临床分析

先天性甲状腺功能减退症在临床并不常见 ,是可以完全治愈的先天性疾病之一 ,但其表现缺乏特异性 ,易误诊。该文总结了 1 980～ 1 998年收治的 46例先天性甲状腺功能减退症患儿的常见临床症状、体征以及实验室检查的结果 ,对治疗情况进行了随访 ,结果表明早期诊断和治疗对其预后具有决定性意义 ,并对其中误诊病例进行了原因分析 ,提出了避免误诊的措施。对早期诊断先天性甲状腺功能减退症防止出现神经精神发育障碍的可能进行了探讨 ,提出了早期诊断先天性甲状腺功能减退症的临床依据。     

小儿先天性甲状腺功能减退症46例临床分析

先天性甲状腺功能减退症在临床并不常见 ,是可以完全治愈的先天性疾病之一 ,但其表现缺乏特异性 ,易误诊。该文总结了 1 980～ 1 998年收治的 46例先天性甲状腺功能减退症患儿的常见临床症状、体征以及实验室检查的结果 ,对治疗情况进行了随访 ,结果表明早期诊断和治疗对其预后具有决定性意义 ,并对其中误诊病例进行了原因分析 ,提出了避免误诊的措施。对早期诊断先天性甲状腺功能减退症防止出现神经精神发育障碍的可能进行了探讨 ,提出了早期诊断先天性甲状腺功能减退症的临床依据。     

�����Լ�״�ٹ��ܼ���֢���״���״󻼶� ��״���򵰰׻���ͻ���о�

??Abstract??Objective To identify thyroglobulin ?? TG?? gene mutation in patients with congenital hypothyroidism with goiter??in order to provide full evidence for gene diagnosis of congenital hypothyroidism. Methods Totally 11 patients with congenital hypothyroidism with goiter in Qingdao Women and Children hospital from Jan. 2012 to Aug. 2012 were enrolled in this study. The 7??14??22??33 and 38 exons of TG gene were amplified through PCR and the products were sequenced directly. The type and characteristic of TG gene mutation in patients with congenital hypothyroidism with goiter in this region were analyzed. Results Two single nucleotide polymorphism of TG gene were identified??but no gene mutation was observed. TG c.3218-81T??G ??rs 853324??homozygous??in 1 patient and c.3218-81T??G??rs 853324??heterozygosis??in 6 patients were found. Conclusion The incidence of TG gene mutation is very low in patients with congenital hypothyroidism with goiter from Qingdao City. It suggests that TG gene mutation may not serve as the mutation hotspot gene of congenital hypothyroidism with goiter in Qingdao City??     

Etiologic diagnosis of congenital hypothyroidism and plasma thyroglobulin

Plasma thyroglobulin (Tg) measurement at the time of screening has a great value in the classification of congenital thyroid defects. Tg was measured in a group of 100 children with congenital hypothyroidism (athyreosis n = 15, ectopic n = 59, eutopic n = 26). Tg was undetectable in athyreosis. These values were significantly different (2.46 +/- 2.52 ng/ml) from those in the group of ectopic (111 +/- 139 ng/ml) and in the group of eutopic (196 +/- 312.1 ng/ml). Four patients with eutopic glands had non measurable Tg and may represent cases with congenital Tg defect.     

Congenital hypothyroidism caused by a novel homozygous mutation in the thyroglobulin gene

Congenital hypothyroidism (CH) due to thyroglobulin (TG) deficit is an autosomal recessive disease (OMIM #274700) characterized by hypothyroidism, goiter, low serum TG, and a negative perchlorate discharge test. The aim of this study was to perform the genetic analysis of the TG gene in two sisters born from consanguineus parents and affected by CH and low serum TG levels. The index patient and her sister were identified at neonatal screening for CH and treated with L-thyroxine (L-T4). After discontinuation of L-T4 therapy, hypothyroidism was confirmed, serum TG was undetectable, and no organification defect after ¹²³I scintigraphy and perchlorate test was shown; thyroid ultrasound showed a eutopic gland of normal size. DNA was extracted from peripheral white blood cells of the two sisters and the father. All 48 exons of TG gene were amplified by polymerase chain reaction and subjected to direct sequencing. A novel homozygous point mutation in exon 10 of TG gene was identified in the patient and her sister. The mutation determined a stop codon at position 768 (R768X) resulting in an early truncated protein or in the complete absence of the protein. The father (euthyroid) was heterozygous carrier of the mutation. Conclusion: Genetic analysis of TG gene was performed in two sisters affected by CH. A novel point mutation of the TG gene determining a stop codon at position 768 of the protein was identified. The early truncated nonfunctioning protein or the absence of the protein due to the premature degradation of abnormal mRNA may be responsible of the observed phenotype.     

甲状腺相关基因突变与先天性甲状腺功能低下症

先天性甲状腺功能低下症(CH)是引起儿童生长和神经发育障碍的常见内分泌疾病,主要由先天性甲状腺发育异常或甲状腺激素合成异常所致。近年来研究发现,部分CH患者存在甲状腺发育或甲状腺素合成相关基因的突变,文章就上述基因的生物学功能,基因突变患者的临床特征作一介绍。     

暂时性甲状腺功能减低伴甲状腺肿大患儿DUOX2基因突变的研究

目的 研究暂时性先天性甲状腺功能减退伴甲状腺肿大患者DUOX2基因突变情况.方法 对5例暂时性甲状腺功能减低伴甲状腺肿大患者DUOX2基因的全部外显子进行基因突变筛查,基因突变类型和特点.结果 在1例先天性甲状腺功能减低症( Congenital Hypothyroidism,CH)患儿中发现DUOX2基因一个等位基因的杂合性突变,为第10外显子cDNA的1329位点发生C＞T的突变(c.C1329T),导致第376密码子精氨酸突变为色氨酸(p.Arg376Trp).其他4例CH患儿均没有发现DUOX2基因突变.结论 在先天性甲状腺功能减退患儿中也发现了DUOX2基因的p.Arg376Trp突变,该突变的单个等位基因剂量的改变可能导致先天性甲状腺功能减退.     

先天性甲状腺功能减低症汉族儿童的促甲状腺素受体基因失活突变

目的探讨汉族儿童促甲状腺素受体（TSHR）基因失活突变与先天性甲状腺功能减低症（CH）的相关性。方法（1）选择79例CH汉族儿童（亚临床甲减14例,年龄1～5.5岁,男8例,女6例;甲减65例,年龄1.5～6岁,男27例,女38例）为研究对象;100名正常儿童（男40例,女60例,年龄1～8岁）作为对照组。（2）采用PCR和DNA测序技术检测TSHR基因失活突变。结果（1）79例CH患儿中有1例发生复合杂合子突变,其突变位点为（Pro52Thr／Val689Gly）。1例发生杂合子突变,其突变位点为（Gly245Ser）。30例患儿在第10外显子2181位核苷酸处发生C-G转换（GAC→GAG）,使727位密码子天冬氨酸被谷氨酸代替（Asp727Glu）。47例患儿在第7外显子561位核苷酸处发生T-c转换（AAT→AAc）,相应的187位氨基酸（Asn）不发生改变。（2）33例正常对照儿童在第10外显子2181位核苷酸处发生C-G转换;50例正常对照儿童在第7外显子561位核苷酸处发生T-c转换（AAT→AAc）。结论浙江汉族CH患儿TSHR基因有3个杂合子突变位点：（Pr052Thr）、（Gly245Ser）、（Val689Gly）,第10外显子2181位核苷酸处（GAc→GAG）及第7外显子561位核苷酸处（AAT→AAC）存在TSHR基因多态性。     

先天性甲状腺功能减低症患儿DUOXA2基因突变研究

目的 探讨广州地区先天性甲状腺功能减低症(CH)患儿DUOXA2基因突变特点及其基因型与表型的关系。方法 采用PCR及直接测序法,对2011年至2012年出生、广州市新生儿筛查中心诊断并排除DUOX2基因突变的20例疑似甲状腺激素合成障碍的CH患者进行DUOXA2基因突变分析。结果 20例CH患者中2例为p.Y246X/p.Y246X纯合突变;4例为单等位基因杂合突变:分别为已知致病突变c.413-414ins A携带者2例,p.Y246X携带者1例,新突变p.G79R携带者1例。2~3岁再评估时显示,2例p.Y246X/p.Y246X纯合突变者分别表现为暂时性CH及轻度永久性CH;4例单等位基因突变者,除1例p.Y246X携带者表现为典型永久性CH外,其余3例携带者均为暂时性CH。结论 DUOXA2基因突变是广州地区疑似甲状腺激素合成障碍性CH患儿较常见的分子发病基础,多数表现为暂时性CH,未发现DUOXA2基因型与表型的关系。新突变p.G79R为致病性突变的可能性大。     

先天性Q-T间期延长综合征3型一家系基因突变分析

目的 对一个表现有先天性Q-T间期延长综合征,同时表现有扩张性心肌病、心脏传导障碍性疾病的家系进行相关基因分析,探讨其发病机制.方法 一个中国人3代多表现型的先天性Q-T间期延长综合征家系,采集8名家系成员和100名健康对照血样,采用PCR扩增、DNA直接测序技术进行SCN5A、KCNQ1、KCNH2、LAMIN A/C基因突变分析,采用多聚酶链反应--单链构象多态性进行基因型和表型研究.结果 PCR-DNA直接测序在先证者钠通道SCN5A基因第26号外显子发现了9个碱基CAGAAGCCC缺失突变,该突变位于SCN5A基因DⅢ和DⅣ连接区域,导致第1507位谷氨酰胺、第1508位赖氨酸、第1509位脯氨酸3个氨基酸缺失.家系中患者检出与先证者相同的突变,而家系内参加本研究的健康人和家系外100名健康对照未出现这种突变.结论 SCN5A基因突变是部分先天性Q-T间期延长综合征的分子发病机制,SCN5A基因delQKP1507-1509突变是国内未曾报道过的新突变,国外的相同突变报道仅表现为Q-T间期延长综合征,无其他表型.进一步开展SCN5A delQKP1507-1509突变的功能研究有助于理解相关疾病的分子发病机制.     

The value of neonatal serum thyroglobulin determinations in the follow-up of patients with congenital hypothyroidism

Serum thyroglobulin was determined in 68 newborn infants with positive screening tests for congenital hypothyroidism. In 38 infants the diagnosis was confirmed (patients), but the remaining 30 were euthyroid at follow-up (controls). The mean thyroglobulin concentration at the age of 2 weeks did not differ significantly between the patients and the controls (179 vs. 125 micrograms/l). Thyroid scintigraphy was performed in 15 patients. All seven with thyroid aplasia, based on 99mTc pertechnetate scintigraphy, had measurable thyroglobulin (greater than 2 micrograms/l) and thyroid hormones in their serum. This indicates that total absence of thyroid tissue is very rare in Swedish patients with congenital hypothyroidism. Scintigraphy based on 99mTc does not permit detection of small amounts of thyroid tissue. The neonatal concentrations of thyroglobulin did not correlate with the results of Griffiths test at 3 years and are therefore not useful for prognosis of psychomotor development. We conclude that neonatal measurement of thyroglobulin is of limited value in the follow-up of patients with congenital hypothyroidism.