Novel promoter and exon mutations of the BMPR2 gene in Chinese patients with pulmonary arterial hypertension

European Journal of Human Genetics

Volumn 17, Issue 8, 2009, Pages 1063-1069

  Wang, Hu ^a   Li, Wen ^b   Zhang, Weili ^a   Sun, Kai ^a   Song, Xiaodong ^a   Gao, Shuo ^a   Zhang, Channa ^a   Hui, Rutai ^a   Hu, Hong ^b  

^a PEKING UNION MEDICAL COLLEGE   (China)

^b CHINESE PLA GENERAL HOSPITAL   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ASPARAGINE; BONE MORPHOGENETIC PROTEIN RECEPTOR 2; GLUTAMIC ACID; LEUCINE; LUCIFERASE; SERINE; TRANSCRIPTION FACTOR SP3;

ADULT; ALLELE; AMINO ACID SUBSTITUTION; ARTICLE; BINDING SITE; CHINESE; CLINICAL ARTICLE; EXON; FAMILIAL DISEASE; FEMALE; FRAMESHIFT MUTATION; GENE DELETION; GENE IDENTIFICATION; GENE LOCATION; GENE SEQUENCE; GENETIC SCREENING; GENETIC TRANSCRIPTION; GENETIC VARIABILITY; HETEROZYGOSITY; HUMAN; HUMAN CELL; INTRON; MALE; MISSENSE MUTATION; MUTATIONAL ANALYSIS; NONSENSE MUTATION; NUCLEOTIDE SEQUENCE; PEDIGREE; PRIORITY JOURNAL; PROMOTER REGION; PULMONARY HYPERTENSION; SEQUENCE ANALYSIS;

ADULT; BASE SEQUENCE; BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II; CELLS, CULTURED; CHINA; DNA MUTATIONAL ANALYSIS; EXONS; FEMALE; GENETIC PREDISPOSITION TO DISEASE; HUMANS; HYPERTENSION, PULMONARY; MALE; MUTATION; PEDIGREE; PROMOTER REGIONS, GENETIC; PULMONARY ARTERY; YOUNG ADULT;

EID: 67749084158     PISSN: 10184813     EISSN: 14765438     Source Type: Journal    
DOI: 10.1038/ejhg.2009.3     Document Type: Article

References (41)

1. Rubin LJ: Primary pulmonary hypertension. N Engl J Med 1997; 336: 111-117.
2. Humbert M, Morrell NW, Archer SL et al: Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol 2004; 43: 13S-24S.
3. Humbert M, Sitbon O, Simonneau G: Treatment of pulmonary arterial hypertension. N Engl J Med 2004; 351: 1425-1436.
4. Cool CD, Stewart JS, Werahera P et al: Three-dimensional reconstruction of pulmonary arteries in plexiform pulmonary hypertension using cell-specific markers. Evidence for a dynamic and heterogeneous process of pulmonary endothelial cell growth. Am J Pathol 1999; 155: 411-419.
5. Nichols WC, Koller DL, Slovis B et al: Localization of the gene for familial primary pulmonary hypertension to chromosome 2q31-32. Nat Genet 1997; 15: 277-280.
6. Deng Z, Morse JH, Slager SL et al: Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Am J Hum Genet 2000; 67 737-744.
7. Lane KB, Machado RD, Pauciulo MW et al: Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. The International PPH Consortium. Nat Genet 2000; 26: 81-84.
8. Machado RD, Aldred MA, James V et al: Mutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial hypertension. Hum Mutat 2006; 27: 121-132.
9. Morisaki H, Nakanishi N, Kyotani S, Takashima A, Tomoike H, Morisaki T: BMPR2 mutations found in Japanese patients with familial and sporadic primary pulmonary hypertension. Hum Mutat 2004; 23: 632.
10. Thomson JR, Machado RD, Pauciulo MW et al: Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-beta family. J Med Genet 2000; 37: 741-745.
11. McGoon M, Gutterman D, Steen V et al: Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 2004; 126: 14S-34S.
12. MaAinescu VD, Kohane IS, Riva A: MAPPER: a search engine for the computational identification of putative transcription factor binding sites in multiple genomes. BMC Bioinformatics 2005; 6: 79.
13. Fu LJ, Zhou AQ, Huang MR et al: A novel mutation in the BMPR2 gene in familial pulmonary arterial hypertension. Chin Med J (Engl) 2008; 121: 399-404.
14. Zhicheng J, Lihe L, Zhiyan H et al: Bone morphogenetic protein receptor-II mutation Arg491Trp causes malignant phenotype of familial primary pulmonary hypertension. Biochem Biophys Res Commun 2004; 315: 1033-1038.
15. Koehler R, Grunig E, Pauciulo MW et al: Low frequency of BMPR2 mutations in a German cohort of patients with sporadic idiopathic pulmonary arterial hypertension. J Med Genet 2004; 41: E127.
16. Machado RD, Pauciulo MW, Thomson JR et al: BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Am J Hum Genet 2001; 68: 92-102.
17. Elliott CG, Glissmeyer EW, Havlena GT et al: Relationship of BMPR2 mutations to vasoreactivity in pulmonary arterial hypertension. Circulation 2006; 113: 2509-2515.
18. Humbert M, Deng Z, Simonneau G et al: BMPR2 germline mutations in pulmonary hypertension associated with fenfluramine derivatives. Eur Respir J 2002; 20: 518-523.
19. Harrison RE, Berger R, Haworth SG et al: Transforming growth factor-beta receptor mutations and pulmonary arterial hypertension in childhood. Circulation 2005; 111: 435-441.
20. Uehara R, Suzuki H, Kurokawa N et al: Novel nonsense mutation of the BMPR-II gene in a Japanese patient with familial primary pulmonary hypertension. Pediatr Int 2002; 44: 433-435.
21. Cogan JD, Vnencak-Jones CL, Phillips III JA et al: Gross BMPR2 gene rearrangements constitute a new cause for primary pulmonary hypertension. Genet Med 2005; 7: 169-174.
22. Sankelo M, Flanagan JA, Machado R et al: BMPR2 mutations have short lifetime expectancy in primary pulmonary hypertension. Hum Mutat 2005; 26: 119-124.
23. Roberts KE, McElroy JJ, Wong WP et al: BMPR2 mutations in pulmonary arterial hypertension with congenital heart disease. Eur Respir J 2004; 24: 371-374.
24. Morrell NW, Yang X, Upton PD et al: Altered growth responses of pulmonary artery smooth muscle cells from patients with primary pulmonary hypertension to transforming growth factor- beta(1) and bone morphogenetic proteins. Circulation 2001; 104: 790-795.
25. Rudarakanchana N, Flanagan JA, Chen H et al: Functional analysis of bone morphogenetic protein type II receptor mutations underlying primary pulmonary hypertension. Hum Mol Genet 2002; 11: 1517-1525.
26. Aldred MA, Vijayakrishnan J, James V et al: BMPR2 gene rearrangements account for a significant proportion of mutations in familial and idiopathic pulmonary arterial hypertension. Hum Mutat 2006; 27: 212-213.
27. Trembath RC, Thomson JR, Machado RD et al: Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. N Engl J Med 2001; 345: 325-334.
28. Sugiyama S, Hirota H, Yoshida M et al: Novel insertional mutation in the bone morphogenetic protein receptor type II associated with sporadic primary pulmonary hypertension. Circ J 2004; 68: 592-594.
29. Abramowicz MJ, Van Haecke P, Demedts M, Delcroix M: Primary pulmonary hypertension after amfepramone (diethylpropion) with BMPR2 mutation. Eur Respir J 2003; 22: 560-562.
30. Miyazono K, Maeda T, Imamura T: BMP receptor signaling: transcriptional targets, regulation of signals, and signaling crosstalk. Cytokine Growth Factor Rev 2005; 16: 251-263.
31. Massague J: TGF-beta signal transduction. Annu Rev Biochem 1998; 67: 753-791.
32. Massague J, Seoane J, Wotton D: Smad transcription factors. Genes Dev 2005; 19: 2783-2810.
33. Goumans MJ, Valdimarsdottir G, Itoh S, Rosendahl A, Sideras P, ten Dijke P: Balancing the activation state of the endothelium via two distinct TGF-beta type I receptors. EMBO J 2002; 21: 1743-1753.
34. Itoh S, Thorikay M, Kowanetz M et al: Elucidation of Smad requirement in transforming growth factor-beta type I receptorinduced responses. J Biol Chem 2003; 278: 3751-3761.
35. Jeffery TK, Upton PD, Trembath RC, Morrell NW: BMP4 inhibits proliferation and promotes myocyte differentiation of lung fibroblasts via Smad1 and JNK pathways. Am J Physiol Lung Cell Mol Physiol 2005; 288: L370-L378.
36. Yu PB, Beppu H, Kawai N, Li E, Bloch KD: Bone morphogenetic protein (BMP) type II receptor deletion reveals BMP ligandspecific gain of signaling in pulmonary artery smooth muscle cells. J Biol Chem 2005; 280: 24443-24450.
37. Suske G: The Sp-family of transcription factors. Gene 1999; 238 291-300.
38. Cawley S, Bekiranov S, Ng HH et al: Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell 2004; 116: 499-509.
39. Udvadia AJ, Templeton DJ, Horowitz JM: Functional interactions between the retinoblastoma (Rb) protein and Sp-family members: Superactivation by Rb requires amino acids necessary for growth suppression. Proc Natl Acad Sci USA 1995; 92: 3953-3957.
40. Ihn H, Trojanowska M: Sp3 is a transcriptional activator of the human alpha2(I) collagen gene. Nucleic Acids Res 1997; 25: 3712-3717.
41. Zhao L, Chang LS: The human POLD1 gene. Identification of an upstream activator sequence, activation by Sp1 and Sp3, and cell cycle regulation. J Biol Chem 1997; 272: 4869-4882.