期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

遗传性多发性骨软骨瘤的基因突变筛查及基因型与表型关系的研究 被引量：2

Gene mutation screening and the genotype-phenotype correlation of hereditary multiple exostoses
原文传递
导出
摘要 目的建立HME的基因突变筛查方法,并探讨其基因型与临床表型的关系.方法根据临床诊断将15例HME先证者分为轻度（M）和重度（Ⅰ S、ⅡS、ⅢS）4型,运用PCR扩增产物直接测序法对先证者及其家系成员进行EXT1和EXT2基因序列分析,筛查其EXT1和EX72基因突变,并分析基因型与临床表型之间的关系.结果 15例HME先证者中有9例为EXT1基因突变,6例为EXT2基因突变,其中EXT1基因I8＋2T＞G、c.1182deIG、c.1108G＞T（p.E370X）、c.335de1A、c.361C＞T（p.Q121X）和c.18791881delCAC为国际上新发现的基因突变位点.EXT1基因突变患者临床表型分别为M型2例（22.2%,2/9）、Ⅰ S型2例、ⅡS型4例和ⅢS型1例,而EXT2基因突变患者M型有5例（83.3%,5/6）,另1例为ⅡS型.结论本研究建立了HME准确、简便的EXT1和EXT2基因突变筛查方法,6个EXT1基因突变I8＋2T＞G、c.1182delG、c.1108G＞T（p.E370X）、c.335delA、c.361C＞T（p.Q121X）和c.1879_1881delCAC为国际首次报道,EXT1基因突变患者相比EXT2基因突变患者临床表型要更严重. Objective To establish the method of gene mutation screening for HME and investigate the relationship between genotype and clinical phenotype in HME patients. Methods Fifteen cases of HME probands were divided into the following four subgroups： mild （M） and severe （ Ⅰ S, Ⅱ S, Ⅲ S） according to the clinical diagnosis. DNA samples were obtained from the probands and family members. All of the EXT1 and EXT2 gene exons and their boundary sequences were amplified by PCR, and sequenced by directsequencing. Then the relationship between the genotypes and clinical phenotype was analyzed. Results Among the fifteen cases of HME probands, nine harbored EXT1 gene mutation, while the other 6 were positive for EXT2 gene mutation. Moreover, six novel mutations in EXT1 gene, including I8 ＋ 2T 〉 G, c. 1182delG,c. 1108G 〉T（p. E370X） ,c. 335delA,c. 361C 〉T（p. Q121X） and c. 1879_1881delCAC were identified. In 9 patients with EXT1 gene mutation, 2 （22. 2% ） were M-type, 2 （22. 2% ） were Ⅰ S -type, 4 （44. 4% ）were Ⅱ S-type,and 1 （ 11.1% ） was ⅢS-type. Whereas, 5 cases （83.3%） were M-type and only one case was Ⅱ S-type（ 16. 7% ） in 6 patients with EXT2 gene mutation. Conclusions An accurate and simple gene diagnostic method for HME was established. Six novel EXT1 gene mutations, including I8 ＋ 2T 〉 G,c. 1182delG, c. 1108G 〉T（p. E370X）, c. 335delA, c. 361C 〉T（p. Q121X）and c. 1879_1881delCAC were identified as well. The clinical phenotype of the patients with EXT1 gene mutation was more severe compared to those with EXT2 gene mutations.
作者 王剑 李玉婵 李怀远 郁婷婷 傅启华
机构地区 上海交通大学医学院附属上海儿童医学中心检验科 上海交通大学医学院附属上海儿童医学中心骨科
出处 《中华检验医学杂志》 CAS CSCD 北大核心 2010年第10期926-930,共5页 Chinese Journal of Laboratory Medicine
基金 上海市卫生局科研基金资助项目（2008195）
关键词 外生骨疣 多发性遗传性 N-乙酰氨基葡糖转移酶类 基因 肿瘤抑制 突变 基因型 表型 Exostoses, multiple hereditary N-Acetylglucosaminyltransferase Genes, tumor suppressor Mutation Genotype Phenotype
分类号 R686 [医药卫生—骨科学]
  • 相关文献

参考文献13

  • 1Pannier S,Legeai-Mallet L.Hereditary multiple exostoses and enchondromatosis.Best Pract Res Clin Rheumatol,2008,22:45-54.
  • 2Philippe C,Porter DE,Emerton ME,et al.Mutation screening of the EXT1 and EXT2 genes in patients with hereditary multiple exostoses.Am J Hum,Genet,7997,61:520-528.
  • 3Francannet C,Cohen-Tanugi A,Le Merrer M,et al.Genotypephenotype correlation in hereditary multiple exostoses.J Med Genet,2001,38:430-434.
  • 4傅启华,李玉婵,王剑,王静.遗传性多发性骨软骨瘤EXT基因的一种新突变[J].诊断学理论与实践,2008,7(6):625-627. 被引量：5
  • 5Li Y,Wang D,Wang W,et al.Identification of four novel EXT1 and EXT2 mutatiors in five Chinese pedigrees with hereditary multiple exostoses.Genet Test Mol Biomarkers,2009,13:825-830.
  • 6Van Hul W,Wuyts W,Hendrickx J,et al.Identification of the third EXT-like gene (EXTL 3) belonging to the EXT gene family.Genomics,1998,47:230-237.
  • 7Hameetman L,David G,Yavas A,et al.Decreased EXT expression and intracellular accumulation of heparin sulphate proteoglycan in osteochondromas and peripheral chondrosarcomas.J Pathol,2007,211:399-409.
  • 8Lonie L,Porter DE,Fraser M,et al.Determination of the mutation spectrum of the EXT1/EXT2 genes in British Caucasian patients with multiple osteochondromas,and exclusion of six candidate genes in EXT negative cases.Hum Mutat,2006,27:1160-1165.
  • 9Xu L,Xia J,Jiang H,et al.Mutation analysis of hereditary multiple exostoses in the Chinese.Hum Genet,1999,105:45-50.
  • 10J(a)ger M,Westhoff B,Portier S,et al.Clinical outcome and genotype in patients with hereditary multiple exostoses.J Orthop Res,2007,25:1541-1551.

二级参考文献9

  • 1[1]Philippe C,Porter DE,Emerton ME,et al.Mutation screening of the EXTI and EXT2 genes in patients with hereditary multiple exostoses[J].Am J Hum,Genet,1997,61(3):520-528.
  • 2[2]Wuyts W,van Hul W,de Bouile K,et al.Mutations in the EXT1 and EXT2 genes in hereditary multiple exostoses[J].Am J Hum Genet,1998,62(2):346-354.
  • 3[3]Francannet C,Cohen-Tanugi A,Le MelTer M,et al.Genotype-phenotype correlation in hereditary multiple exostoses[J].J Med C,enet,2001,38(7):430-434.
  • 4[4]Faiyaz-U1-Haque M,Ahmad W,Zaidi S,et al.Novel mutations in the EXT1 gene in two consanguineous families affected with multiple hereditary exostoses (familial osteochondromatosis)[J].Clin Genet,2004,66(2):144-151.
  • 5[5]Van Hul W,Wuyts W,Hendriekx J0 et al.Identification of a third EXT-like gene (EXTL 3) belonging to the EXT gene family[J].Genomics,1998,47(2):230-237.
  • 6[6]Ahn J,Ludecke H J,Lindow S,et al.Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT1)[J].Nat Genet,1995,11(2):137-143.
  • 7[7]Ropero S,Setien F,Espada J,et al.Epigenetic loss of the familial tumor-suppresser gone exostosin-1 (EXT1) disrupts heparan sulfate synthesis in cancer cells[J].Hum Mol Genet,2004,13(22):2753-2765.
  • 8[8]Liu SG,Li FF,Huang SZ,et al.A novel mutation in the EXT2 gene identified in two unrelated Chinese families with hereditary multiple exostoses[J].Genet Test,2007,11(4):445-449.
  • 9[9]Liu SG,Lu DG,Liu ZQ,et al.A novel mutation in EXT2 gene in a Chinese family with hereditary multiple exostoses[J].Genet Test,2008,12(3):331-332.

共引文献4

同被引文献24

引证文献2

二级引证文献5

中华检验医学杂志
2010年 第10期

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部