期刊文献+

两个新RUNX2基因突变引起家族性锁骨颅骨发育不全 被引量:10

Two novel RUNX2 gene mutations in two Chinese families with cleidocranial dysplasia
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摘要 目的探讨RUNX2基因突变在锁骨颅骨发育不全病因研究中的意义及两个中国家族性锁骨颅骨发育不全家系发病的分子机制。方法提取收集到的2个锁骨颅骨发育不全家系中4例患者和4名家系健康成员、102名无关正常对照外周血基因组DNA,应用PCR扩增产物双向直接测序方法检测RUNX2基因第1~7外显子及相邻侧翼区的DNA序列,测序结果与RUNX2基因正常序列对比分析。对发现的突变位点用酶切方法证实。结果测序结果发现一家系中两例父子患者的RUNX2基因第1外显子发生错义突变c.346T〉A(W116R),该错义突变通过Bsr I限制性内切酶对PCR扩增产物行酶切分析得到进一步确认。另一家系中两例患者的RUNX2基因第3外显子发生无义突变c.610A〉T(K204X)。在两个家系中的正常家系成员和无关正常对照RUN2基因DNA序列中没有发现上述突变。结论通过RUNX2基因,检测在中国人群中发现两个RUNX2基因新致病突变,扩展了遗传性锁骨颅骨发育不全的基因突变谱,对阐明该病发病机制及其基因诊断和遗传咨询有重要意义。 Objective To identify the RUNX2 gene mutation in two unrelated Chinese families with cleidocranial dysplasia (CCD), and to assess the feasibility of gene diagnosis for patients with CCD. Methods Genomic DNA was isolated from peripheral blood samples of 4 patients and 4 healthy members in the two pedigrees as well as 102 unrelated healthy controls. All 7 coding exons and their flanking intronic sequences of the RUNX2 gene were amplified by PCR, then the PCR products were sequenced bi-direetionally. The sequencing results were compared with normal sequences in Gengank to identify the mutation. The mutation was confirmed by RFLP with restriction endonuclease. Results In one family, a novel heterozygous missense mutation c. 346T〉A (Wll6R) in exon 1 of the RUNX2 gene was detected in the two affected individuals, and the mutation was further confirmed with Bsr I restriction endonuclease digestion. In the other family, a novel nonsense mutation c. 610A〉T (K204X) was identified in the two patients. No above sequence change was found in the 102 healthy controls. Conclusion Two novel RUNX2 mutations were found in two unrelated Chinese families with cleidocranial dysplasia. The identification of these mutations further extended the mutation spectrum of RUNX2 gene and will facilitate prenatal diagnosis and gene diagnosis of CCD.
出处 《中华医学遗传学杂志》 CAS CSCD 北大核心 2010年第2期140-143,共4页 Chinese Journal of Medical Genetics
关键词 锁骨颅骨发育不全 RUNX2基困 基因突变 cleidocranial dysplasia RUNX 2 gene gene mutation
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参考文献16

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二级参考文献27

  • 1Lee B, Thirunavukkarasu K, Zhou L, et al. Missense mutations abolishing DNA binding of the osteoblast-specific transcription factor OSF2/CBFA1 in cleidocranial dysplasia. Nat Genet, 1997, 16:307-310.
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  • 6Quack B, Vonderstrass M, Aylsworth AS, et al. Mutation analysis of core binding factor a1 in patients with cleidocranial dysplasia. Am J Hum Genet, 1999, 65:1268-1278.
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共引文献21

同被引文献25

  • 1焦智慧,陈义兵,赵振华,吴庆华,任淑敏,孔祥东.两个锁骨颅骨发育不良家系的RUNX2基因变异分析及产前诊断[J].中华医学遗传学杂志,2019,36(12):1179-1182. 被引量:1
  • 2高超,吴丽,耿香菊,宋丽佳.先天性颅锁骨发育不全家系分析[J].中国实用神经疾病杂志,2010,13(23):54-55. 被引量:3
  • 3王莹,吴华,张晓霞,赵红珊,冯海兰.家族性锁骨颅骨发育不全的基因突变检测[J].中华口腔医学杂志,2005,40(6):459-462. 被引量:20
  • 4Pamuk ON, Mundlos S, Cakir N. Cleidocranial dyspla- sia in a mother and her two children [ J ]. Joint Bone Spine ,2008,75 ( 6 ) :725-727.
  • 5Gilbert I, He XF, Faimer P, et al, Expression of the osteoblast differentiation factor RUNX2 is inhibited by TNFα [ J ]. J Biol Chern, 2002,277 ( 4 ) : 2695 -2701.
  • 6Kim HJ, Nam S H, Kim H J. Four novel RUNX2 mu- tations including a splice donor site result in the cleido- cranial dysplasia phenotype [ J ]. J Cell Physiol, 2006, 207( 1 ) :114-122.
  • 7Baumert U, Golan I, Redlich M, et al. Cleidoeranial dysplasia: molecular genetic analysis and phenotypic - based description of a Middle European patient group [ J ]. Am J Med Genet, 2005,139 A ( 2 ) : 78 -85.
  • 8Yoshida T, Kanegane H, Osato M, et al. Functional a- nalysis of RUNX2 Mutations in Japanese patients with cleidocranial dysplasia demonstrates novel genotype - phenotype correlations [ J]. Am J Hum Genet, 2002,71 (4) :724-738.
  • 9Ogawa E, Maruyama M, Kagoshima H, et al. PEBP2/PEA2 represen*s a family of transcription factors homologous to the products of the Drosophila runt gene and the human AMLI gene[J]. Proc Natl Acad Sci USA, 1993,90:6 859-6 863.
  • 10Kim HJ, Nam SH, Kim HJ, et al. Four novel RUNX2 muta- tions including a splice donor site result in the cleidocranial dys- plasia phenotype[J]. J Cell Physiol,2006, 207,114-122.

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