Mosaic ACVRL1 and ENG mutations in hereditary haemorrhagic telangiectasia patients

被引：30

作者：

Best, D. Hunter ^{[1
,2
]}

Vaughn, Cecily ^{[1
]}

McDonald, Jamie ^{[2
,3
]}

Damjanovich, Kristy ^{[1
]}

Runo, James R. ^{[3
,4
]}

Chibuk, Jason M. ^{[5
]}

Bayrak-Toydemir, Pinar ^{[1
,2
]}

机构：

[1] ARUP Labs, ARUP Inst Clin Expt Pathol, Salt Lake City, UT 84108 USA

[2] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA

[3] Univ Utah, Dept Radiol, HHT Ctr, Salt Lake City, UT 84132 USA

[4] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA

[5] Univ Calif San Diego, Dept Med, Div Med Genet, La Jolla, CA 92093 USA

来源：

JOURNAL OF MEDICAL GENETICS | 2011年 / 48卷 / 05期

关键词：

JUVENILE POLYPOSIS; HYPERTENSION; PHENOTYPE; GENOTYPE; LOCUS; MAPS;

D O I：

10.1136/jmg.2010.088286

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder caused by mutations in the ACVRL1, ENG, and SMAD4 genes. HHT is commonly characterised by small arteriovenous malformations (AVMs) known as telangiectasias of the skin, oral or gastrointestinal mucosa, as well as larger AVMs of solid organs (lungs, liver, brain). However, the manifestations of HHT are extremely variable. Two patients with no family history of HHT and strikingly different clinical presentations, who are mosaic for mutations in the ACVRL1 or ENG gene, are reported here. These cases represent the first report of mosaicism in patients clinically affected with classical HHT and pulmonary arterial hypertension, and suggest the need for awareness of mosaicism when performing clinical testing for this disorder.

引用

页码：358 / 360

页数：3

共 11 条

[1] High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome [J].

Aretz, S. ;

Stienen, D. ;

Uhlhaas, S. ;

Stolte, M. ;

Entius, M. M. ;

Loff, S. ;

Back, W. ;

Kaufmann, A. ;

Keller, K-M ;

Blaas, S. H. ;

Siebert, R. ;

Vogt, S. ;

Spranger, S. ;

Holinski-Feder, E. ;

Sunde, L. ;

Propping, P. ;

Friedl, W. .

JOURNAL OF MEDICAL GENETICS, 2007, 44 (11) :702-709

[2] A fourth locus for hereditary hemorrhagic telangiectasia maps to chromosome 7 [J].

Bayrak-Toydemir, Pinar ;

McDonald, Jamie ;

Alkarsu, Nurten ;

Toydemir, Reha M. ;

Calderon, Fernanda ;

Tuncali, Timur ;

Tang, Wei ;

Miller, Franklin ;

Mao, Rong .

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2006, 140A (20) :2155-2162

[3] Novel mutations in ENG and ACVRL1 identified in a series of 200 individuals undergoing clinical genetic testing for hereditary hemorrhagic telangiectasia (HHT):: Correlation of genotype with phenotype [J].

Bossler, Aaron D. ;

Richards, Jennifer ;

George, Cicily ;

Godmilow, Lynn ;

Ganguly, Arupa .

HUMAN MUTATION, 2006, 27 (07) :667-675

[4] A new locus for hereditary haemorrhagic telangiectasia (HHT3) maps to chromosome 5 [J].

Cole, SG ;

Begbie, ME ;

Wallace, GMF ;

Shovlin, CL .

JOURNAL OF MEDICAL GENETICS, 2005, 42 (07) :577-582

[5] International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia [J].

Faughnan, M. E. ;

Palda, V. A. ;

Garcia-Tsao, G. ;

Geisthoff, U. W. ;

McDonald, J. ;

Proctor, D. D. ;

Spears, J. ;

Brown, D. H. ;

Buscarini, E. ;

Chesnutt, M. S. ;

Cottin, V. ;

Ganguly, A. ;

Gossage, J. R. ;

Guttmacher, A. E. ;

Hyland, R. H. ;

Kennedy, S. J. ;

Korzenik, J. ;

Mager, J. J. ;

Ozanne, A. P. ;

Piccirillo, J. F. ;

Picus, D. ;

Plauchu, H. ;

Porteous, M. E. M. ;

Pyeritz, R. E. ;

Ross, D. A. ;

Sabba, C. ;

Swanson, K. ;

Terry, P. ;

Wallace, M. C. ;

Westermann, C. J. J. ;

White, R. I. ;

Young, L. H. ;

Zarrabeitia, R. .

JOURNAL OF MEDICAL GENETICS, 2011, 48 (02) :73-87

[6] A combined syndrome of juvenile polyposis and hereditary haemorrhagic telanglectasia associated with mutations in MADH4 (SMAD4) [J].

Gallione, CJ ;

Repetto, GM ;

Legius, E ;

Rustgi, AK ;

Schelley, SL ;

Tejpar, S ;

Mitchell, G ;

Drouin, É ;

Westermann, CJJ ;

Marchuk, DA .

LANCET, 2004, 363 (9412) :852-859

[7] Clinical and analytical sensitivities in hereditary hemorrhagic telangiectasia testing and a report of de novo mutations [J].

Gedge, Friederike ;

McDonald, Jamie ;

Phansalkar, Amit ;

Chou, Lan-Szu ;

Calderon, Fernanda ;

Mao, Rong ;

Lyon, Elaine ;

Bayrak-Toydemir, Pinar .

JOURNAL OF MOLECULAR DIAGNOSTICS, 2007, 9 (02) :258-265

[8] Transforming growth factor-β receptor mutations and pulmonary arterial hypertension in childhood [J].

Harrison, RE ;

Berger, R ;

Haworth, SG ;

Tulloh, R ;

Mache, CJ ;

Morrell, NW ;

Aldred, MA ;

Trembath, RC .

CIRCULATION, 2005, 111 (04) :435-441

[9] Multiple Sequence Variants in Hereditary Hemorrhagic Telangiectasia Cases Illustration of Complexity in Molecular Diagnostic Interpretation [J].

McDonald, Jamie ;

Gedge, Friederike ;

Burdette, Allene ;

Carlisle, James ;

Bukjiok, Changkuoth Jock ;

Fox, Michelle ;

Bayrak-Toydemir, Pinar .

JOURNAL OF MOLECULAR DIAGNOSTICS, 2009, 11 (06) :569-582

[10] Hereditary haemorrhagic telangiectasia Pathophysiology, diagnosis and treatment [J].

Shovlin, Claire L. .

BLOOD REVIEWS, 2010, 24 (06) :203-219

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