雄激素受体基因(CAG)n重复多态性与先天性尿道下裂的关系

目的 了解雄激素受体基因(CAG)n重复多态性与先天性尿道下裂的形成的关系。方法 应用PCR技术提取26例先天性尿道下裂患儿和20例对照组男性雄激素受体基因第一外显子中含(CAG)n重复多态性的DNA片段，运用DNA自动测序准确了解CAG重复次数，比较两组间CAG重复片段的均数差别。结果 尿道下裂组和对照组间CAG重复片段有显著差异，并发现2例尿道下裂患儿CAG重复片段为38及42。结论 雄激素受体基因第一外显子上CAG重复多态性与尿道下裂的发生可能存在一定关系。     

特发性矮小患儿生长激素受体基因Ex3多态性与重组人生长激素疗效分析

目的：观察生长激素受体（GHR）基因Ex3多态性与重组人生长激素（rhGH）治疗青春期前特发性矮小（ISS）疗效间的相关性。方法：青春期前ISS患儿30例,均采用rhGH［0.116±0.02 IU/(kg/d)］治疗;其外周血白细胞中抽提基因组DNA,采用多重PCR扩增GHR基因Ex3区域。对不同基因型患儿治疗后生长速率（GV）、年龄对应身高标准差积分（HtSDSCA）及骨龄对应身高标准差积分（HtSDSBA）、预测终身高进行比较。结果：rhGH治疗半年后d3/d3基因型组GV较fl/fl基因型组明显增加［（6.3±1.6）cm/年 vs （3.4±0.5）cm/年,P<0.05］。结论：ISS患儿GHR Ex3基因型与rhGH促生长疗效存在一定关联,d3/d3等位基因型患儿用rhGH治疗后生长速率明显优于fl/fl等位基因型。［中国当代儿科杂志,2010,12（9）：730-733］     

生长激素受体基因突变与非生长激素缺乏性矮身材的相关研究

目的了解生长激素受体（GHR）基因突变与非生长激素缺乏性矮小的相关性,以及GHR基因突变患儿的临床特点。方法（1）选择47例（男33例,女14例,年龄2—16岁）非生长激素缺乏而又显著矮小的患儿作为研究对象;80例身高正常的儿童（男49例,女31例,年龄1—17岁）作为对照组。（2）应用PCR-SSCP和基因测序技术检测GHR突变。（3）通过家系成员和正常对照人群的基因分析以及氨基酸同源序列分析等,推测突变基因的性质。结果（1）在47例矮小患儿中有5例、4种不同的GHR基因突变：H56R、G148E、IVS6-30,-31CA〉TG和IVS8＋10G〉C。5例患儿均为杂合突变,杂合突变个体的检出频率为10．6％（5／47）。（2）对照组的基因分析显示这些突变非多态性改变,初步认为H56R和G148E突变可能对蛋白功能产生影响。（3）确定了1种多态性突变：G168G（GGA〉GGG）。该位点基因频率的分布在矮小儿童组和正常对照组之间的差异无统计学意义,但与西方白种人之间的差异有统计学意义。提示该突变可能是单核苷酸多态性改变,与身高没有相关关系。但该位点的等位基因存在人种的差异。结论非生长激素缺乏性矮身材患儿存在GHR基因杂合突变。     

维生素D受体多态性与晚发性佝偻病易感性研究

目的研究维生素D受体基因起始密码子（VDRSC）多态性在晚发性佝偻病组、维生素D缺乏状态组及正常对照组中分布频率的差异,探讨晚发性佝偻病的遗传易感因素。方法用聚合酶链反应——限制性长度多态性（RFLP）分析晚发性佝偻病组30例、维生素D缺乏状态组35例以及正常对照组60例VDRSC多态性的分布频率。结果三组VDRSC基因型分布频率差异有统计学意义（χ^2=13．184,P=0．010）;等位基因分布频率差异也有统计学意义（χ^2=8．975,P=0．011）。组间两两比较晚发性佝偻病组VDRSC基因型和等位基因与其他两组比较差异有统计学意义,其FF型频率（56．7％）明显高于正常对照组（21．7％,P=0．006）,也明显高于维生素D缺乏状态组（22．9％,P=0．002）;晚发性佝偻病组F型（70．0％）明显高于正常对照组（48．3％,P=0．006）,也明显高于维生素D缺乏状态组（47．1％,P=0．009）。多项分类Logistic回归分析结果显示,在调整了其他危险因素后,FF型仍是晚发性佝偻病的危险因素,相对危险度（OR）=3．120。结论VDRSC多态性可能决定晚发性佝偻病的遗传易感性。     

哮喘与白细胞介素-4受体信号传导及其受体基因多态性

哮喘是一种慢性气道炎症。调控变应性炎症和气道重建的一个关键途径涉及白细胞介素-4(IL-4),其受体组件中的亚单位——IL-4受体α亚单位(IL-4Rα)作为IL-4的中间信号,起着枢纽作用,是细胞因子信号传导的基础。IL-4Rα的基因变异与哮喘和特应性相关,人类IL-4Rα基因编码顺序也与哮喘和特应性的易感性相关。目前已经证实一些定位IL-4Rα信号基因序列导致的氨基酸置换可能参与信号的转换。近年来有关IL-4R基因多态性与哮喘、特应性疾病以及呼吸道合胞病毒的相关研究证实,IL-4Rα基因是哮喘和特应性的重要候选基因。现将近年来有关研究作一综述。     

肺炎支原体P1基因多态性分析现状

在肺炎支原体（MP）感染中，黏附宿主呼吸道上皮细胞和成功定植是感染的关键一步，黏附通过MP表面的P1蛋白介导与宿主细胞的分子受体结合。传统上基于川基因序列的变异将MP分为两型，新近研究表明，在川基因上有2个特异的重复序列，一个重复序列被命名为RepMP4，位于编码区的5’末端，另一个为RepMP2／3，位于3’末端。针对这两个重复序列的PER扩增，结果用限制性内切酶分析，使分型更为细致，共检出8个亚型，这表明在P1基因型中存在着更多的亚型。用基因的变异可能通过重复序列之间的重组出现在MP染色体其他的位置上而发生。通过直接测序法对临床分离株川基因更为广泛的研究可做出更精确的分型，以进一步了解用基因多态性的现状。     

呼吸道合胞病毒毛细支气管炎基因多态性的研究进展

呼吸道合胞病毒（RSV）是婴幼儿呼吸道感染最常见的病原。感染RSV以后多数患儿仅表现为上呼吸道感染，而少数则出现需住院治疗的严重毛细支气管炎（毛支）和肺炎。导致这种病情差异的原因尚不清楚，随着对其遗传学研究的不断深入，通过对RSV毛支患儿基因型的分析．发现白细胞介素-8，4，10和表面活性蛋白等均存在基因多态性，且与RSV毛支的疾病易感性、病情严重程度等相关。     

维生素D受体基因多态性对儿童骨密度影响的研究

儿童阶段骨密度持续增长,是影响成年骨峰值的关键时期。防治儿童期低骨密度是减少成年后骨质疏松发生的重要环节。遗传是决定骨密度的重要因素之一,其中维生素D受体(VDR)的基因多态性对儿童骨密度的影响是近年来国外研究的热点。目前发现与骨密度相关的VDR四个等位基因分别对应内切酶BsmI、ApaI、TaqI、FokI的酶切位点。但世界各地的研究结果不一致,可能与种族差异、环境因素、研究方法各不相同有关。本文综合各种观点,分析造成这种不一致的可能原因,提示在研究VDR基因多态性与骨密度关系时应综合考虑的因素。     

生长激素受体基因异常及多态性与特发性矮小的关系研究进展

随着促生长激素释放激素-生长激素-胰岛素样生长因子(GHRH-GH-IGF-1)轴和基因学研究的深入,生长激素受体基因(GHR基因)的突变及其核苷酸多态性与特发性矮小(ISS)的关系逐渐明了.GHR基因异常多发生在生长激素受体(GHR)蛋白的胞外区,可引起细胞内信号转导障碍,导致GHR蛋白功能及表达部分缺失,生长激素不能完全发挥作用或部分不敏感,从而可能发生ISS; GHR基因单核苷酸多态性(SNP),尤其是外显子Ex3多态性与ISS易感性有关.此外,GHR基因异常及SNP与ISS中IGF-1、生长激素结合蛋白血清水平及重组人生长激素治疗效果密切相关.深入研究ISS中GHR候选基因的筛查、蛋白功能表达及SNP分析,有利于提高ISS的遗传诊断水平,对明确ISS的病因及指导临床治疗具有重要意义.     

CD14基因多态性与儿童特应性疾病的相关性

目的研究脂多糖受体基因（CD14）多态性在温州地区汉族儿童中的分布特征及其与特应性疾病的关联。方法特应征组113例,病例入选符合下列标准：（1）年龄2～12岁的汉族儿童;（2）临床诊断为哮喘、过敏性鼻炎或特应性皮炎;（3）血清总IgE升高;（4）血清特异性IgE阳性。选取2～12岁正常体检儿童79例为对照组。应用免疫荧光法测定血清总IsE,UniCAP系统测定sIgE。应用测序法测定两组儿童CD14基因序列,寻找多态位点,调查多态位点的分布特征,比较两组儿童多态位点的基因型频率和等位基因频率,比较不同基因型的血浆IgE水平。结果（1）特应征组和对照组儿童均发现CD141—159多态性,以TT基因型为主,未发现其他多态位点。其中对照组儿童TT、TC、CC3种基因型频率分别为57．0％、28．0％和15．0％,特应征组儿童TT、TC、CC3种基因型频率分别为46.9％、35．4％和17．7％,按Hardy-Weinberg平衡吻合度检验,差异无统计学意义（x^2=3．462,P〉0．05）。两组的基因型频率和等位基因频率分布差异无统计学意义（x^2=1．918,P〉0．05）。（2）不同性别间基因型频率差异无统计学意义（x^2=3．458,P〉0．05）。（3）经对数转换,CD14/—159CC基因型、TC基因型和TT基因型的血清IgE分别为（2500±460）IU／L、（2400±460）IU／L、（2520±460）IU／L,方差分析差异无统计学意义（F=0．807,P〉0．05）。结论（1）温州地区汉族儿童存在CD141—159多态性,未发现CD14基因其他多态位点。温州地区汉族儿童CD141—159基因型以TT为主。（2）未发现CD141—159基因型和特应征发病及IgE水平之间的关联。     

Phenotype and Radiological Correlation in Patients with Growth Hormone Deficiency

Objective  

To confirm that MRI findings like hypoplastic anterior pituitary, thin or interrupted pituitary stalk, and ectopic posterior pituitary (EPP) in patients with growth hormone deficiency are a good indicator of the severity of hypopituitarism.     

The Dosage Dependency of Growth and Maturity in Growth Hormone Deficiency Treated with Human Growth Hormone

ABSTRACT. A group of 11 pre-pubertal growth hormone deficient patients were treated with human growth hormone over a period of 4 years. In 6 of the patients the dosage was 4 IU 3 times a week and in 5, 8 IU 3 times a week. Changes in height demonstrated that the "catch up" was significantly greater and of longer duration in the second group. In spite of a more rapid increase of bone age in the second group, the prognosis of final height had improved significantly at the end of the study period. A comparative study of the plasma concentrations of T4, T SH, gonadotrophins and steroids, to see if the greater velocity of bone maturity in the second group could be due to contamination of the preparation by other could be due to contamination of the preparation by other hypophysary hormones, did not demonstrate significant differences between the groups.     

Growth Hormone Releasing Hormone in the Assessment and Long-term Treatment of Growth Hormone Deficiency

The secretion of hGH after the administration of the analogue of growth hormone releasing hormone, GHRH (1–29)NH₂, to 8 normal adults and 41 short children has been studied. The children were classified on the basis of their hGH response to insulin-induced hypoglycaemia; 28 had severe hGH deficiency (peak serum hGH less than 7 mIU/litre) and 13 had simple short stature (peak serum hGH greater than 15 mIU/litre). The hGH response to GHRH was similar in normal adults and short stature children, but significantly lower in the hGH deficient children. In 23 (82%) of the hGH deficient children the peak serum hGH in response to GHRH was greater than 7 mIU/litre (the maximum value seen during hypoglycaemia), and in 14 (50%) the peak serum hGH in response to GHRH was greater than 15 mIU/litre. This suggests that in the majority of hGH deficient children the defect in hGH secretion results from hypothalamic GHRH deficiency. The hGH responses of the short stature children to insulin-induced hypoglycaemia were mainly in the low range of normal, and the majority showed normal hGH responses to GHRH. Eighteen prepubertal children with definite hGH deficiency have been treated for 3–18 months with twice daily, subcutaneous injections of GHRH. This has promoted linear growth in 12 children, of whom 8 showed an increment in height velocity of 2–11 cm/year. GHRH provides a valuable method for the assessment of hGH secretion, but by itself it cannot be used to establish deficient hGH secretion; this requires a stimulation test that promotes hypothalamic GHRH secretion, such as insulin-induced hypoglycaemia. GHRH is a practical alternative therapy to hGH for some hGH-deficient children.     

生长激素运动筛查试验与生长激素激发试验对生长激素缺乏症诊断价值的比较

目的 评价生长激素(GH)运动筛查试验和GH激发试验对儿童生长激素缺乏症的诊断价值.方法 选取200例身材矮小患儿,均符合身材矮小诊断标准,无骨代谢、糖尿病等其他内分泌代谢疾病.对患儿均进行GH运动筛查试验及GH激发试验.GH激发试验包括精氨酸激发试验、左旋多巴激发试验及胰岛素激发试验,本研究中所有患儿在3种GH激发试验中任选2种.2种试验均采用放射免疫法进行检测.结果 身材矮小患儿行GH运动试验和GH激发试验的GH峰值强度分别为(12.78±6.98) μg/L和(14.07±5.89) μg/L,二者GH峰值比较无显著性差异(t=1.87 P>0.05).200例患儿中GH激发试验和运动试验均阳性者29例;运动试验阳性而GH激发试验阴性者5例,运动试验存在2.5%假阳性率.2种试验方法阳性率间比较无统计学差异(χ2=0.47 P>0.05).结论 GH运动筛查试验和GH激发试验得出的结果具有很高的一致性.由于运动试验具有操作简单、安全等优点,应将GH运动筛查试验作为身材矮小患儿的首选筛查试验.     

Growth Hormone Secretion and Growth Hormone Treatment in Children with Intrauterine Growth Retardation

Albertsson-Wikland, K. (Departments of Paediatrics II and Physiology, University of Gothenburg, Gothenburg, Sweden). Growth hormone secretion and growth hormone treatment in children with intrauterine growth retardation. Acta Paediatr Scand [Suppl] 349: 35, 1989.
Few children with intrauterine growth retardation (IUGR) fail to show catch-up growth during the first year of life. There may he many reasons for this, ranging from disturbances of hormone production to hormonal unresponsiveness of target cells. This report presents preliminary data on growth hormone (GH) secretion and responses to GH treatment in 16 children with IUGR and poor catch-up growth, six of whom had Silver-Russell stigmata. GH secretion was assessed by measurement of the GH response to an arginine-insulin test and determination of spontaneous GH secretion over 24 hours. GH production was heterogeneous hut, more often than expected, children showed both a low response to GH provocation and low spontaneous secretion of GH. Five out of six of the children with Silver-Russell syndrome and seven out of 10 of the children with non-Silver-Russell IUGR gained more than 2 cm in height during 1 year of treatment with GH at a dose of 0.1 IU/kg/day. These results clearly demonstrate that some children with IUGR and poor catch-up growth secrete insufficient amounts of GH, and that many of these very short children show an improvement in growth rate during treatment with physiological doses of GH.     

Growth Hormone and Leukemia

With improved survival of children with cancer, attention has focused on late effects of therapy. Among the most clinically bothersome of these is short stature, seen in children in whom cranial radiation has induced growth hormone (GH) deficiency. Some of these children (notably those with a history of acute lymphocytic leukemia or brain tumor) have been treated with and benefited from supplemental GH.