Study on DUOXA2 gene mutation in patients with congenital hypothyroidism and goiter.

doi:10.11852/zgetbjzz2015-23-01-03

journal1 ›› 2015, Vol. 23 ›› Issue (1): 7-10.DOI: 10.11852/zgetbjzz2015-23-01-03

Previous Articles Next Articles

Study on DUOXA2 gene mutation in patients with congenital hypothyroidism and goiter.

LIU Lu¹,LI Hui-chao²,CHAI Jian³,SHAO Hui-ying⁴,YI Ming-ji⁵,CHEN Pei-jie¹,LIU Shi-guo⁵,YAN Sheng-li¹

1 Department of Endocrinology; 2 Department of Thyroid Surgery,the Affiliated Hospital of Qingdao University,Qingdao,Shandong 266003,China; 3 Department of Biochemistry and Molecular Biology,Medical College of Qingdao University,Qingdao,Shandong 266003,China; 4 Hospital of Traditional Chinese Medicine of Pingyi,Linyi,Shandong 273300,China; 5 Department of Pediatrics; 6 Prenatal Diagnosis Center,the Affiliated Hospital of Qingdao University,Qingdao,Shandong 266003,China

Received:2014-08-04 Online:2015-01-10 Published:2015-01-10
Contact: YAN Sheng-li,E-mail:yansl07@163.com

先天性甲状腺功能减退症伴甲状腺肿大患儿DUOXA2基因突变研究

刘璐¹,李惠超²,柴健³,邵慧莹⁴,衣明纪⁵ ,陈培杰¹,刘世国⁶,阎胜利¹

1 青岛大学附属医院内分泌科,山东青岛 266003; 2 青岛大学附属医院甲状腺外科,山东青岛 266003;3 青岛大学医学院生物化学与分子生物学,山东青岛 266021; 4 临沂市平邑县中医院五官科,山东临沂 273300; 5 青岛大学附属医院儿童保健科,山东青岛 266003; 6 青岛大学附属医院产前诊断中心,山东青岛 266003

通讯作者: 阎胜利,E-mail:yansl07@163.com
作者简介:刘璐(1989-),女,山东人,硕士研究生在读,主要研究方向为内分泌
基金资助:
国家自然科学基金(81170812);山东省人口和计划生育委员会科技计划项目(2013-5)

Abstract

Abstract: Objective To investigate the dual oxidase maturation factor 2 (DUOXA2) mutations in patients with congenital hypothyroidism (CH) and goiter from Shandong province,China,and to give solid theoretical basis for prenatal diagnosis and gene therapy of CH. Methods A total of 55 patients of CH with goiter and 100 healthy individuals were enrolled,and extracted Genomic DNA from peripheral blood leukocytes.All exons of DUOXA2 gene were amplified by PCR,the products were directly sequenced to find new mutations types of DUOXA2 gene,and χ² test was used. Results A homozygous nonsense mutation (c.C738G) of DUOXA2 gene was identified in one patient,and a SNP (rs2576092,IVS4+6 C>T) in intron 4 was found in 10 CH patients and 13 healthy controls.There was no significant difference between the SNP rate in CH patients and controls(P＞0.05). Conclusion The mutation rate of DUOXA2 gene is very low,which suggests that DUOXA2 gene mutation may not be the main cause of CH with goiter patients from Shandong province.

Key words: congenital hypothyroidism, goiter, DUOXA2 gene, gene mutation, single nucleotide polymorphism

摘要： 目的研究中国山东地区先天性甲状腺功能减退症(congenital hypothyroidism,CH)伴甲状腺肿大患儿双氧化酶成熟因子2(DUOXA2)基因突变类型及特点,为CH的诊断及治疗提供理论依据。方法选取55例CH伴甲状腺肿大患儿和100例正常对照。提取外周静脉血基因组DNA,采用PCR扩增与直接测序的方法,对DUOXA2基因全部外显子进行突变筛查。对发现的SNP位点的基因频率进行χ² 检验。结果在1例CH患者中发现1个DUOXA2基因纯合性无义突变(c.C738G)。并在10例CH患儿和13个健康人中发现1个单核苷酸多态性(SNP)位点(rs2576092,IVS4+6 C>T)。在正常对照中未发现突变。两组的SNP基因频率比较,差异无统计学意义。结论 DUOXA2基因突变率较低,可能不是山东地区CH伴甲状腺肿大患者的主要病因。

关键词: 先天性甲状腺功能减退症, 甲状腺肿大, DUOXA2基因, 突变, 单核苷酸多态性

CLC Number:

R725.8

LIU Lu,LI Hui-chao,CHAI Jian,SHAO Hui-ying,YI Ming-ji,CHEN Pei-jie,LIU Shi-guo,YAN Sheng-li. Study on DUOXA2 gene mutation in patients with congenital hypothyroidism and goiter.[J]. journal1, 2015, 23(1): 7-10.

刘璐,李惠超,柴健,邵慧莹,衣明纪 ,陈培杰,刘世国,阎胜利. 先天性甲状腺功能减退症伴甲状腺肿大患儿DUOXA2基因突变研究[J]. 中国儿童保健杂志, 2015, 23(1): 7-10.

References

[1] 张伯昕,李小芳,余毅震.北京地区新生儿先天性甲状腺功能低下症发病趋势研究[J].中国儿童保健杂志,2014,22 (7):742-745.
[2] Rastogi MV,LaFranchi SH.Congenital hypothyroidism[J].Orphanet J Rare Dis,2010,10:5-17.
[3] BaVN,Cangul H,Agladioglu SY,et al.Mild and severe congenital primary hypothyroidism in two patients by thyrotropin receptor (TSHR) gene mutation[J].J Pediatr Endocrinol Metab,2012,25(11-12):1153-1156.
[4] Carvalho A,Hermanns P,Rodrigues AL,et al.A new PAX8 mutation causing congenital hypothyroidism in three generations of a family is associated with abnormalities in the urogenital tract[J].Thyroid,2013,23(9):1074-1078.
[5] Nakamura K,Sekijima Y,Nagamatsu K,et al.A novel nonsense mutation in the TITF-1 gene in a Japanese family with benign hereditary chorea[J].J Neurol Sci,2012,313(1-2):189-192.
[6] Moreno JC,Visser TJ.Genetics and phenomics of hypothyroidism and goiter due to iodotyrosine deiodinase (DEHAL1) gene mutations[J].Mol Cell Endocrinol,2010,322(1-2):91-98.
[7] Medeiros-Neto G,Targovnik HM,Vassart G.Defective thyroglobulin synthesis and secretion causing goiter and hypothyroidism[J].Endocr Rev,1993,14(2):165-183.
[8] Altmann K,Hermanns P,Mühlenberg R,et al.Congenital goitrous primary hypothyroidism in two German families caused by novel thyroid peroxidase (TPO) gene mutations [J].Exp Clin Endocrinol Diabetes,2013,121(6):343-346.
[9] De Marco G,Agretti P,Montanelli L,et al.Identification and functional analysis of novel dual oxidase 2 (DUOX2) mutations in children with congenital or subclinical hypothyroidism[J].J Clin Endocrinol Metab,2011,96(8):e1335-1339.
[10] Hulur I,Hermanns P,Nestoris C,et al.A single copy of the recently identified dual oxidase maturation factor (DUOXA) 1 gene produces only mild transient hypothyroidism in a patient with a novel biallelic DUOXA2 mutation and monoallelic DUOXA1 deletion[J].J Clin Endocrinol Metab,2011,96(5):e841-845.
[11] Van Sande J,Dequanter D,Lothaire P,et al.Thyrotropin stimulates the generation of inositol1,4,5-trisphosphate in human thyroid cells[J].J Clin Endocrinol Metab,2006,91(3):1099-1107.
[12] Zamproni I,Grasberger H,Cortinovis F,et al.Biallelic inactivation of the dual oxidase maturation factor 2(DUOXA2) gene as a novel cause of congenital hypothyroidism[J].J Clin Endocrinol Metab,2008,93(2):605-610.
[13] 梁德武,牟红梅,张玲,等.安康市先天性甲状腺功能减低症筛查状况与治疗分析[J].中国儿童保健杂志,2014,22(7):739-741.
[14] Grasberger H,Refetoff S.Genetic causes of congenital hypothyroidism due to dyshormonogenesis[J].Curr Opin Pediatr,2011,23(4):421-428.
[15] Ohye H,Sugawara M.Dual oxidase,hydrogen peroxide and thyroid diseases[J].Exp Biol Med (Maywood),2010,235(4):424-433.
[16] Yi RH,Zhu WB,Yang LY,et al.A novel dual oxidase maturation factor 2 gene mutation for congenital hypothyroidism[J].Int J Mol Med,2013,31(2):467-470.

Study on DUOXA2 gene mutation in patients with congenital hypothyroidism and goiter.

先天性甲状腺功能减退症伴甲状腺肿大患儿DUOXA2基因突变研究

PDF

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

[1]	CHEN Yi-ru, CHEN Wen-xiong. Research progress in neurodevelopmental disorder caused by KIF5C gene mutation [J]. Chinese Journal of Child Health Care, 2023, 31(2): 171-175.
[2]	XIAO Wu-cai, LIU Zheng, CHEN Jing, WANG Hui, SONG Jie-yun, ZHOU Shuang, GAO Ai-yu, ZHANG Fang, WANG Hai-jun. Relationship between rs2241423 polymorphism of MAP2K5 gene and intervention effect of childhood obesity [J]. Chinese Journal of Child Health Care, 2022, 30(9): 952-955.
[3]	LI Si-xiu, LIU Ping, DENG Jia, CHEN Jia-lei, MAO Dan-dan, HU Wen-guang. Case report and literature review on PPP2R1A gene mutation-associated intellectual disability, microcephalus and corpus callosum agenesis [J]. Chinese Journal of Child Health Care, 2022, 30(7): 809-812.
[4]	SHANG Li, XU Pei-ru, AIERKEN Aibibai, WANG Yi-lin. Association of the single nucleotide polymorphism of NOS3 gene with obesity in children aged 6~13 years [J]. Chinese Journal of Child Health Care, 2022, 30(5): 490-494.
[5]	YANG Li-juan, DENG Gao, DING Bo, YANG Li-min, LI Dong-ming, HUANG Yong-fang, LIN Na. Association of ADAM33 gene and its serum level with the risk of asthma in Zhuang children in Guangxi [J]. Chinese Journal of Child Health Care, 2022, 30(11): 1185-1190.
[6]	ZHU Mei-jun, JI Ju-hua, ZHU Jie, SONG Lei, ZHOU Feng, ZHAO Jin-hua. Study on the correlation between DNA load of drug-resistance mycoplasma pneumoniae and 23sRNA mutation at 2063 locus in children [J]. Chinese Journal of Child Health Care, 2021, 29(9): 1017-1020.
[7]	JIANG Xiang, XU Ai-jing, TANG Fang, JIA Xue-fang, TANG Cheng-fang, CHEN Qian-yu, ZHENG Rui-dan, LIU Ji-lian, HUANG Yong-lan. Application of auto regressive integrated moving average model in predicting the incidence of congenital hypothyroidism in Guangzhou [J]. Chinese Journal of Child Health Care, 2021, 29(4): 425-429.
[8]	ZHANG Xue-mei, XIE Bang-gui, CHEN Xiao-bing, PAN Cai-qin, LU Yu-zhu, LI Jun-ke, CHEN Qiu-ning. Analysis of the influencing factors for congenital hypothyroidism in 45 infants [J]. Chinese Journal of Child Health Care, 2021, 29(11): 1233-1236.
[9]	ZHANG Ya-guo, YE Piao, OU Ming-cai, YANG Yun-xia, CHEN Xue-lian, YANG Li-juan. Genetic analysis of 43 children with hyperphenylalaninemia in some regions of Sichuan [J]. journal1, 2020, 28(11): 1255-1258.
[10]	ZHAO Xiao-fen, ZHOU Xing, ZHANG Yan, HU Hao, QIU Li-ling, LI Yang-fang. Association between interleukin-1β single nucleotide polymorphisms and sepsis in full-term neonates [J]. journal1, 2020, 28(1): 65-68.
[11]	SUN Ying-mei, SONG Dong-po, WANG Wei-qing, LI Wen-jie. Analysis on the diagnosis,treatment and gene mutation of neonatal primary carnitine deficiency [J]. journal1, 2019, 27(8): 820-823.
[12]	TAN Jian-qiang, YAN Ti-zhen, HUANG Jun, TANG Ning, YUAN De-jian, CAI Ren. Analysis on clinical characteristics and gene mutation of children with X-linked severe combined immunodeficiency [J]. journal1, 2019, 27(4): 439-442.
[13]	SUN Ying-mei, YU Chun-dong, LYU Jin-feng, LYU Ya-nan, LI Wen-jie. Analysis of gene mutation characteristics of medium chain acyl-CoA dehydrogenase deficiency by neonatal screening [J]. journal1, 2019, 27(10): 1071-1074.
[14]	WANG Li-wen, NI Min, LIU Su-na, JIA Chen-lu, LUO Chun-wei, ZHAO De-hua. Evaluation of the performance of genetic screening processor and setting the cut-off values in screening for congenital hypothyroidism in newborns [J]. journal1, 2019, 27(10): 1147-1150.
[15]	LONG Wei, YANG Yu-qi, ZHOU Wen-bai,GUO Fang,ZHOU Hong,ZHANG Bin, LIU Jian-bing, YU Bin. Effect of hypothyroidism in pregnancy on thyroid stimulating hormone of heel blood in neonates [J]. journal1, 2018, 26(8): 839-842.