Analysis of ENG and ACVRL1 genes in 137 HHT Italian families identifies 76 different mutations (24 novel). Comparison with other European studies

Journal of Human Genetics

Volumn 52, Issue 10, 2007, Pages 820-829

  Olivieri, Carla ^a   Pagella, Fabio ^b   Semino, Lucia ^b   Lanzarini, Luca ^b   Valacca, Cristina ^a   Pilotto, Andrea ^b   Corno, Sabrina ^b   Scappaticci, Susi ^a   Manfredi, Guido ^c   Buscarini, Elisabetta ^c   Danesino, Cesare ^a,b  

^a UNIVERSITY OF PAVIA   (Italy)

^b FONDAZIONE IRCCS POLICLINICO SAN MATTEO   (Italy)

^c MAGGIORE HOSPITAL   (Italy)

Author keywords

ACVRL1 mutation; ENG mutation; Hereditary hemorrhagic telangiectasia; HHT

Indexed keywords

ACVRL1 GENE; ARTICLE; CONTROLLED STUDY; DENATURING HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; ENG GENE; ETHNICITY; EUROPE; GENE; GENE MUTATION; HUMAN; ITALY; MAJOR CLINICAL STUDY; MISSENSE MUTATION; RENDU OSLER WEBER DISEASE; SINGLE STRAND CONFORMATION POLYMORPHISM;

ACTIVIN RECEPTORS, TYPE II; ANTIGENS, CD; DNA MUTATIONAL ANALYSIS; EUROPEAN CONTINENTAL ANCESTRY GROUP; FEMALE; HUMANS; ITALY; MALE; MUTATION, MISSENSE; POLYMORPHISM, GENETIC; RECEPTORS, CELL SURFACE; RNA SPLICE SITES; TELANGIECTASIA, HEREDITARY HEMORRHAGIC;

EID: 34848865319     PISSN: 14345161     EISSN: None     Source Type: Journal    
DOI: 10.1007/s10038-007-0187-5     Document Type: Article

References (53)

1. Abdalla SA, Letarte M (2006) Hereditary haemorrhagic telangiectasia: current views on genetics and mechanisms of disease. J Med Genet 43:97-110
2. Abdalla SA, Pece-Barbara N, Vera S, Tapia E, Paez E, Bernabeu C, Letarte M (2000) Analysis of ALK-1 and endoglin in newborns from families with hereditary hemorrhagic telangiectasia type 2. Hum Mol Genet 9:1227-1237
3. Abdalla SA, Cymerman U, Johnson RM, Deber CM, Letarte M (2003) Disease-associated mutations in conserved residues of ALK-1 kinase domain. Eur J Hum Genet 11:279-287
4. Abdalla SA, Gallione CJ, Barst RJ, Horn EM, Knowles JA, Marchuk DA, Letarte M, Morse JH (2004) Primary pulmonary hypertension in families with hereditary haemorrhagic telangiectasia. Eur Respir J 23:373-377
5. Abdalla SA, Cymerman U, Rushlow D, Chen N, Stoeber GP, Lemire EG, Letarte M (2005) Novel mutations and polymorphisms in genes causing hereditary hemorrhagic telangiectasia. Hum Mutat 25:320-321
6. Arthur HM, Ure J, Smith AJ, Renforth G, Wilson DI, Torsney E, Charlton R, Parums DV, Jowett T, Marchuk DA, Burn J, Diamond AG (2000) Endoglin, an ancillary TGFbeta receptor, is required for extraembryonic angiogenesis and plays a key role in heart development. Dev Biol 217:42-53
7. Bayrak-Toydemir P, McDonald J, Akarsu N, Toydemir RM, Calderon F, Tuncali T, Tang W, Miller F, Mao R (2006a) A fourth locus for hereditary hemorrhagic telangiectasia maps to chromosome 7. Am J Med Genet A 140:2155-2162
8. Bayrak-Toydemir P, McDonald J, Markewitz B, Lewin S, Miller F, Chou LS, Gedge F, Tang W, Coon H, Mao R (2006b) Genotype-phenotype correlation in hereditary hemorrhagic telangiectasia: Mutations and manifestations. Am J Med Genet 140A:463-470
9. Berg JN, Gallione CJ, Stenzel TT, Johnson DW, Allen WP, Schwartz CE, Jackson CE, Porteous ME, Marchuk DA (1997) The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2. Am J Hum Genet 61:60-67
10. Bossler AD, Richards J, George C, Godmilow L, Ganguly A (2006) 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. Hum Mutat 27:667-675
11. Bourdeau A, Faughnan ME, Letarte M (2000) Endoglin-deficient mice, a unique model to study hereditary hemorrhagic telangiectasia. Trends Cardiovasc Med 10:279-285
12. Brusgaard K, Kjeldsen AD, Poulsen L, Moss H, Vase P, Rasmussen K, Kruse TA, Horder M (2004) Mutations in endoglin and in activin receptor-like kinase 1 among Danish patients with hereditary haemorrhagic telangiectasia. Clin Genet 66:556-561
13. Carmel I, Tal S, Vig I, Ast G (2004) Comparative analysis detects dependencies among the 5′ splice-site positions. RNA 10: 828-840
14. Cole SG, Begbie ME, Wallace GM, Shovlin CL (2005) A new locus for hereditary haemorrhagic telangiectasia (HHT3) maps to chromosome 5. J Med Genet 42:577-582
15. Cymerman U, Vera S, Pece-Barbara N, Bourdeau A, White RI Jr, Dunn J, Letarte M (2000) Identification of hereditary hemorrhagic telangiectasia type 1 in newborns by protein expression and mutation analysis of endoglin. Pediatr Res 47:24-35
16. Cymerman U, Vera S, Karabegovic A, Abdalla S, Letarte M (2003) Characterization of 17 novel endoglin mutations associated with hereditary hemorrhagic telangiectasia. Hum Mutat 21:482-492
17. David L, Mallet C, Mazerbourg S, Feige JJ, Bailly S (2007) Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells. Blood 109:1953-1961
18. den Dunnen JT, Antonarakis SE (2000) Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat 15:7-12
19. Fernandez-L A, Sanz-Rodriguez F, Zarrabeitia R, Perez-Molino A, Hebbel RP, Nguyen J, Bernabeu C, Botella LM (2005) Blood outgrowth endothelial cells from Hereditary Haemorrhagic Telangiectasia patients reveal abnormalities compatible with vascular lesions. Cardiovasc Res 68:235-248
20. Fernandez-L A, Sanz-Rodriguez F, Zarrabeitia R, Perez-Molino A, Morales C, Restrepo CM, Ramirez JR, Coto E, Lenato GM, Bernabeu C, Botella LM (2006) Mutation study of Spanish patients with hereditary hemorrhagic telangiectasia and expression analysis of Endoglin and ALK1. Hum Mutat 27:295
21. Gallione CJ, Klaus DJ, Yeh EY, Stenzel TT, Xue Y, Anthony KB, McAllister KA, Baldwin MA, Berg JN, Lux A, Smith JD, Vary CP, Craigen WJ, Westermann CJ, Warner ML, Miller YE, Jackson CE, Guttmacher AE, Marchuk DA (1998) Mutation and expression analysis of the endoglin gene in hereditary hemorrhagic telangiectasia reveals null alleles. Hum Mutat 11:286-294
22. Gallione CJ, Scheessele EA, Reinhardt D, Duits AJ, Berg JN, Westermann CJ, Marchuk DA (2000) Two common endoglin mutations in families with hereditary hemorrhagic telangiectasia in the Netherlands Antilles: evidence for a founder effect. Hum Genet 107:40-44
23. Gallione CJ, Repetto GM, Legius E, Rustgi AK, Schelley SL, Tejpar S, Mitchell G, Drouin E, Westermann CJ, Marchuk DA (2004) A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). Lancet 363:852-859
24. Gallione CJ, Richards JA, Letteboer TG, Rushlow D, Prigoda NL, Leedom TP, Ganguly A, Castells A, Ploos van Amstel JK, Westermann CJ, Pyeritz RE, Marchuk DA (2006) SMAD4 mutations found in unselected HHT patients. J Med Genet 43:793-797
25. Gu Y, Jin P, Zhang L, Zhao X, Gao X, Ning Y, Meng A, Chen YG (2006) Functional analysis of mutations in the kinase domain of the TGF-beta receptor ALK1 reveals different mechanisms for induction of hereditary hemorrhagic telangiectasia. Blood 107:1951-1954
26. Harrison RE, Flanagan JA, Sankelo M, Abdalla SA, Rowell J, Machado RD, Elliott CG, Robbins IM, Olschewski H, McLaughlin V, Gruenig E, Kermeen F, Halme M, Raisanen-Sokolowski A, Laitinen T, Morrell NW, Trembath RC (2003) Molecular and functional analysis identifies ALK-1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia. J Med Genet 40:865-871
27. Johnson DW, Berg JN, Baldwin MA, Gallione CJ, Marondel I, Yoon SJ, Stenzel TT, Speer M, Pericak-Vance MA, Diamond A, Guttmacher AE, Jackson CE, Attisano L, Kucherlapati R, Porteous ME, Marchuk DA (1996) Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nat Genet 13:189-195
28. Karabegovic A, Shinawi M, Cymerman U, Letarte M (2004) No live individual homozygous for a novel endoglin mutation was found in a consanguineous Arab family with hereditary haemorrhagic telangiectasia. J Med Genet 41:e119
29. Kjeldsen AD, Moller TR, Brusgaard K, Vase P, Andersen PE (2005) Clinical symptoms according to genotype amongst patients with hereditary haemorrhagic telangiectasia. J Intern Med 258:349-355
30. Klaus DJ, Gallione CJ, Anthony K, Yeh EY, Yu J, Lux A, Johnson DW, Marchuk DA (1998) Novel missense and frameshift mutations in the activin receptor-like kinase-1 gene in hereditary hemorrhagic telangiectasia. Hum Mutat 12:137, MIB n. 164
31. Kuehl HK, Caselitz M, Hasenkamp S, Wagner S, El-Harith el-HA, Manns MP, Stuhrmann M (2005) Hepatic manifestation is associated with ALK1 in hereditary hemorrhagic telangiectasia: identification of five novel ALK1 and one novel ENG mutations. Hum Mutat 25(3):320
32. Lastella P, Sabba C, Lenato GM, Resta N, Lattanzi W, Gallitelli M, Cirulli A, Guanti G (2003) Endoglin gene mutations and polymorphisms in Italian patients with hereditary haemorrhagic telangiectasia. Clin Genet 63:536-540
33. Lenato GM, Lastella P, Di Giacomo MC, Resta N, Suppressa P, Pasculli G, Sabba C, Guanti G (2006) DHPLC-based mutation analysis of ENG and ALK-1 genes in HHT Italian population. Hum Mutat 27:213-214
34. Lesca G, Plauchu H, Coulet F, Lefebvre S, Plessis G, Odent S, Riviere S, Leheup B, Goizet C, Carette MF, Cordier JF, Pinson S, Soubrier F, Calender A, Giraud S; French Rendu-Osler Network (2004) Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France. Hum Mutat 23:289-299
35. Lesca G, Burnichon N, Raux G, Tosi M, Pinson S, Marion MJ, Babin E, Gilbert-Dussardier B, Riviere S, Goizet C, Faivre L, Plauchu H, Frebourg T, Calender A, Giraud S; French Rendu-Osler Network (2006) Distribution of ENG and ACVRL1 (ALK1) mutations in French HHT patients. Hum Mutat 27:598
36. Lesca G, Olivieri C, Burnichon N, Pagella F, Carette MF, Gilbert-Dussardier B, Goizet C, Roume J, Rabilloud M, Saurin JC, Cottin V, Honnorat J, Coulet F, Giraud S, Calender A, Danesino C, Buscarini E, Plauchu H; French-Italian Rendu-Osler Network (2007) Genotype-phenotype correlations in hereditary hemorrhagic telangiectasia: data from the French-Italian HHT network. Genet Med 9:14-22
37. Letteboer TG, Zewald RA, Kamping EJ, de Haas G, Mager JJ, Snijder RJ, Lindhout D, Hennekam FA, Westermann CJ, Ploos van Amstel JK (2005) Hereditary hemorrhagic telangiectasia: ENG and ALK-1 mutations in Dutch patients. Hum Genet 116:8-16
38. Letteboer TG, Mager HJ, Snijder RJ, Koeleman BP, Lindhout D, Ploos van Amstel HK, Westermann KJ (2006) Genotype-phenotype relationship in Hereditary Hemorrhagic Telangiectasia. J Med Genet 43:371-377
39. McAllister KA, Baldwin MA, Thukkani AK, Gallione CJ, Berg JN, Porteous ME, Guttmacher AE, Marchuk DA (1995) Six novel mutations in the endoglin gene in hereditary hemorrhagic telangiectasia type 1 suggest a dominant-negative effect of receptor function. Hum Mol Genet 4:1983-1985
40. Olivieri C, Mira E, Delu G, Pagella F, Zambelli A, Malvezzi L, Buscarini E, Danesino C (2002) Identification of 13 new mutations in the ACVRL1 gene in a group of 52 unselected Italian patients affected by hereditary haemorrhagic telangiectasia. J Med Genet 39:E39
41. Olivieri C, Lanzarini L, Pagella F, Semino L, Corno S, Valacca C, Plauchu H, Lesca G, Barthelet M, Buscarini E, Danesino C (2006) Echocardiographic screening discloses increased values of pulmonary artery systolic pressure in 9 of 68 unselected patients affected with hereditary hemorrhagic telangiectasia. Genet Med 8:183-190
42. Paquet ME, Pece-Barbara N, Vera S, Cymerman U, Karabegovic A, Shovlin C, Letarte M (2001) Analysis of several endoglin mutants reveals no endogenous mature or secreted protein capable of interfering with normal endoglin function. Hum Mol Genet 10:1347-1357
43. Pece N, Vera S, Cymerman U, White RI Jr, Wrana JL, Letarte M (1997) Mutant endoglin in hereditary hemorrhagic telangiectasia type 1 is transiently expressed intracellularly and is not a dominant negative. J Clin Invest 100:2568-2579
44. Prigoda NL, Savas S, Abdalla SA, Piovesan B, Rushlow D, Vandezande K, Zhang E, Ozcelik H, Gallie BL, Letarte M (2006) Hereditary haemorrhagic telangiectasia: mutation detection, test sensitivity and novel mutations. J Med Genet 43:722-728
45. Ravnic-Glavač M, Glavač D, Dean M (1994) Sensitivity of single strand conformation polymorphism and heteroduplex method for mutation detection in the cystic fibrosis gene. Hum Mol Genet 3: 801-807
46. Roca X, Sachidanandam R, Krainer AR (2003) Intrinsic differences between authentic and cryptic 5′ splice sites. Nucleic Acids Res 31:6321-6333
47. Schulte C, Geisthoff U, Lux A, Kupka S, Zenner HP, Blin N, Pfister M (2005) High frequency of ENG and ALK1/ACVRL1 mutations in German HHT patients. Hum Mutat 25:595
48. Shapiro MB, Senapathy P (1987) RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression. Nucleic Acids Res 15:7155-7174
49. Shovlin CL, Hughes JM, Scott J, Seidman CE, Seidman JG (1997) Characterization of endoglin and identification of novel mutations in hereditary hemorrhagic telangiectasia. Am J Hum Genet 61:68-79
50. Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, Kjeldsen AD, Plauchu H (2000) Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet 91:66-67
51. Trembath RC, Thomson JR, Machado RD, Morgan NV, Atkinson C, Winship I, Simonneau G, Galie N, Loyd JE, Humbert M, Nichols WC, Morrell NW, Berg J, Manes A, McGaughran J, Pauciulo M, Wheeler L (2001) Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. N Engl J Med 345:325-334
52. Wehner LE, Folz BJ, Argyriou L, Twelkemeyer S, Teske U, Geisthoff UW, Werner JA, Engel W, Nayernia K (2006) Mutation analysis in hereditary haemorrhagic telangiectasia in Germany reveals 11 novel ENG and 12 novel ACVRL1/ALK1 mutations. Clin Genet 69:239-245
53. Yeo G, Burge CB (2004) Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals. J Comput Biol 11:377-394