遗传性出血性毛细血管扩张症致严重鼻出血的早期基因诊断

籍灵超; 王志新; 王倩; 张静; 贾婧杰; 尤少华; 白银; 周雪筠; 赵素萍; 周颖; 张革化; 王洪田

doi:10.13201/j.issn.1001-1781.2013.05.021

遗传性出血性毛细血管扩张症致严重鼻出血的早期基因诊断

- 1 解放军总医院耳鼻咽喉头颈外科(北京, 100853);
- 2 辽宁省凌源监狱管理分局中心医院耳鼻咽喉科;
- 3 中山大学附属第三医院耳鼻咽喉头颈外科
基金项目:
军队“十一五”科技攻关课题(No:08G128)

详细信息

通讯作者: 张革化; 王洪田

中图分类号: R765.23

收稿日期: 2012-12-06

Early genetic diagnosis in patients with HHT induced severe nosebleed

- 1 Department of Otolaryngology-Head and Neck Surgery, Chinese PLA General Hospital, Beijing, 100853, China;
- 2 Department of Otolaryngology, Liaoning Lingyuan Prison Branch Administration Central Hospital;
- 3 Department of Otolaryngology-Head and Neck Surgery, the Third Affiliated Hospital of Sun Yat-sen University

More Information

Corresponding authors: ZHANG Gehua ; WANG Hongtian

Received Date: 06 December 2012

摘要

摘要: 目的: 探讨遗传性出血性毛细血管扩张症(HHT)致严重鼻出血的早期基因诊断。方法: 对2个HHT家系共23例成员进行详细的临床检查及评估,提取外周静脉血DNA,聚合酶链反应扩增目的基因ENG和ACVRL-1,测序并进行序列分析,判断突变的致病性。结果: NMG-1家系采集到静脉血标本的11例中有6例携带ACVRL-1基因的错义突变c.263A>G。GD-2家系采集到静脉血标本的12例中有5例携带ACVRL-1基因的错义突变c.199C>G。有鼻出血病史者突变基因检出率为100%,无鼻出血者史突变基因检出率为25%。结论: 基因诊断极高的灵敏度和特异性在HHT早期诊断中具有重要的应用价值,可成为临床常规检测项目。
- 鼻出血 /
- 遗传性出血性毛细血管扩张症 /
- 基因 /
- 诊断
Abstract: Objective: To study the early gene diagnosis of hereditary hemorrhagic telangiectasia(HHT) induced severe nosebleed.Method: Clinical features of 23 family members in two HHT pedigrees were examined. Genomic DNA was extracted from peripheral blood samples. PCR amplification was conducted to screen ENG and ACVRL-1 genes with their specific primers. Direct sequencing was performed to detect the mutation. Mutation analysis was carried out to evaluate its significance.Result: A heterozygous c.263A>G mutation was identified in exon 3 of ACVRL-1 in 6 out of 11 members in NMG-1 pedigree. In GD-2 pedigree, 5 of 11 members carried c.199C>G mutation. Mutation detection rate was 100% in subjects with nosebleed history and 25% in family members without epistaxis.Conclusion: Gene diagnosis characterized by high sensitivity and specificity is of great practical significance and early genetic screening should be a clinical routine test for HHT induced severe nosebleed.
- nosebleed /
- hereditary hemorrhagic telangiectasia /
- gene /
- diagnosis

HTML全文

参考文献(16)

[1]	GUTTMATCHER A E,MARCCHUK D A,WHITE R IJr.Hereditary haemorrhages telangiectasia[J].New EngJ Med,1995,333:918-924.
[2]	GEDGE F,MCDONALD J,PHANSALKAR A,et al.Clin-ical and analytical sensitivities in hereditary hemorrhagictelangiectasia testing and a report of de novo mutations[J].J Mol Diagn,2007,9:258-265.
[3]	OLIVIERI C,MIRA E,DELÙG,et al.Identification of 13 new mutations in the ACVRL1 gene in a group of 52unselected Italian patients affected by hereditary haemor-rhagic telangiectasia[J].J Med Genet,2003,39:145-148.
[4]	NG P C,HENIKOFF S.Accounting for human polymor-phisms predicted to affect protein function[J].GenomeRes,2002,12:436-446.
[5]	贾婧杰,张静,赵立东,等.Ⅱ型遗传性毛细血管扩张症临床特点和ACVRL1基因筛查[J].中华医学杂志,2012,92(16):1107-1111.
[6]	SHOVLIN C L,GUTTMACHER A E,BUSCARINI E,etal.Diagnostic criteria for hereditary hemorrhagic telangi-ectasia(Rendu-Osler-Weber Syndrome)[J].Am J MedGenet,2000,91:66-67.
[7]	MCGEE T L,SEYEDAHMADI B J,SWEENEY M O,et al.Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome typeⅡor non-syn-dromic retinitis pigmentosa[J].J Med Genet,2010,47:499-506.
[8]	GIORDANO P,NIGRO A,LENATO G M,et al.Screening for children from families with Rendu-Osler-Weber disease:from geneticist to clinician[J].JThromb Haemost,2006,4:1237-1245.
[9]	PLAUCHU H,CHADAREVIAN J P,BIDEAU A,et al.Age-Related clinical profile of hereditary hemorrhagictelangiectasia in an epidemiologically recruited popula-tion[J].Am J Med Genet,1989,32:291-297.
[10]	ABDALLA S A,LETARTE M.Hereditary haemorrhagictelangiectasia:current views on genetics and mechanismsof disease[J].J Med Genet,2006,43:97-110.
[11]	田佳新,周兵,许康,等.遗传性出血性毛细血管扩张症一家系ALKl基因突变研究和临床微创治疗[J].中国耳鼻咽喉头颈外科,2009,16(4):209-213.
[12]	WAITE K A,ENG C.From developmental disorder toheritable cancer:it's all in the BMP/TGF-β family[J].Nat Rev Genet,2003,4:763-773.
[13]	FAUGHNAN M E,PALDA V A,GARCIA-TSAO G,etal.International guidelines for the diagnosis and manage-ment of hereditary hemorrhagic telangiectasia[J].J MedGenet,2011,48:73-87.
[14]	SCOTTI C,OLIVIERI C,BOERI L,et al.Bioinformatic a-nalysis of pathogenic missense mutations of activin recep-tor like kinase 1 ectodomain[J].PLoS One,2011,6:e26431-e26431.
[15]	LEBRIN F,SRUN S,RAYMOND K,et al.Thalidomidestimulates vessel maturation and reduces epistaxis in in-dividuals with hereditary hemorrhagic telangiectasia[J].Nat Med,2010,4:420-428.
[16]	BENZINOU M,CLERMONT F,LETTEBOER T,et al.Mouse and human strategies identify PTPN14 as a modi-fier of angiogenesis and hereditary haemorrhagic telangi-ectasia[J].Nat Commun,2012,3:616-621.