Hostname: page-component-848d4c4894-sjtt6 Total loading time: 0 Render date: 2024-06-22T18:49:08.910Z Has data issue: false hasContentIssue false
  • English
  • Français

The mendelian basis of congenital heart defects

Published online by Cambridge University Press:  19 August 2008

Bruno Dallapiccola ,
Bruno Marino ,
Maria Cristina Digilio ,
Rita Mingarelli ,
Giuseppe Novelli  and
Aldo Giannotti
Bruno Dallapiccola
Affiliation:
From the Chair of Human Genetics, Tor Vergata University, Rome, Pediatric Cardiology and Medical Genetics, Bambino Gesu Hospital, Rome and C.S.S. Hospital, San Giovanni Rotondo
Bruno Marino*
Affiliation:
From the Chair of Human Genetics, Tor Vergata University, Rome, Pediatric Cardiology and Medical Genetics, Bambino Gesu Hospital, Rome and C.S.S. Hospital, San Giovanni Rotondo
Maria Cristina Digilio
Affiliation:
From the Chair of Human Genetics, Tor Vergata University, Rome, Pediatric Cardiology and Medical Genetics, Bambino Gesu Hospital, Rome and C.S.S. Hospital, San Giovanni Rotondo
Rita Mingarelli
Affiliation:
From the Chair of Human Genetics, Tor Vergata University, Rome, Pediatric Cardiology and Medical Genetics, Bambino Gesu Hospital, Rome and C.S.S. Hospital, San Giovanni Rotondo
Giuseppe Novelli
Affiliation:
From the Chair of Human Genetics, Tor Vergata University, Rome, Pediatric Cardiology and Medical Genetics, Bambino Gesu Hospital, Rome and C.S.S. Hospital, San Giovanni Rotondo
Aldo Giannotti
Affiliation:
From the Chair of Human Genetics, Tor Vergata University, Rome, Pediatric Cardiology and Medical Genetics, Bambino Gesu Hospital, Rome and C.S.S. Hospital, San Giovanni Rotondo
*
Prof. Bruno Dallapiccola, Dipartimento di Sanita Pubblica e Biologia Cellulare, Universit´ Tor Vergata, Via di Tor Vergata, 1–00133 Roma, Italia. Tel. 396-72596080; Fax. 396-20427313.
Get access Rights & Permissions [Opens in a new window]

Abstract

The revolution in molecular genetics is contributing to the understanding of normal and abnormal cardiovascular development and morphogenesis. Recent investigations have shown that a growing number of congenital heart malformations is due to single gene defects. The combined contribution of clinical and molecular studies is providing the chromosomal map of the genes related to these isolated cardiac defects, and to syndromes characteristically associated with specific cardiac malformations. These advances are relevant to clinical practice, since the accumulated knowledge can improve the quality of management of affected patients.

Keywords

Congenital heart defectgenesmolecular biology
Type
Review Article
Information
Cardiology in the Young , Volume 6 , Issue 4 , October 1996 , pp. 264 - 271
Copyright
Copyright © Cambridge University Press 1996

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Ferencz, C, Boughman, JA, Neill, CA, Brenner, JI, Perry, LW. Congenital cardiovascular malformations: Questions on inheritance. J Am Coll Cardiol 1989; 14: 756–763.CrossRefGoogle ScholarPubMed
2.Nora, JJ. Causes of congenital heart diseases: Old and new modes, mechanisms, and models. Am Heart J 1993; 125: 1409–1419.Google Scholar
3.Nora, JJ. Multifactorial inheritance hypothesis for the etiology of congenital heart diseases. The genetic-environmental interaction. Circulation 1968; 38: 604–617.Google Scholar
4.Nora, JJ, Nora, AH. The evolution of specific genetic and environmental counseling in congenital heart diseases. Circulation 1978; 57: 205–213.CrossRefGoogle ScholarPubMed
5.Nora, JJ, Meyer, TC. Familial nature of congenital heart diseases. Pediatrics 1966; 37: 329–334.Google Scholar
6.Mori, K, Ando, M, Takao, A. Genetic aspects of congenital heart disease. Japan Circul J 1973; 37: 35–39.Google Scholar
7.Corone, P, Bonaiti, C, Feingold, J, Fromont, S, Berthet-Bondet, D. Familial congenital heart disease: How are the various types related? Am J Cardiol 1983; 51: 942–945.Google Scholar
8.Ferencz, C. The etiology of congenital cardiovascular malformations: Observations on genetic risks with implications for further birth defects research. J Med 1985; 16: 497–508.Google ScholarPubMed
9.Boughman, JA, Berg, KA, Astemborski, JA, Clark, EB, McCarter, RJ, Rubin, JD, Ferencz, C. Familial risks of congenital heart defect assessed in a population-based epidemiologic study. Am J Med Genet 1987; 26: 839–849.Google Scholar
10.Nora, JJ, Nora, AH. Update on counseling the family with a first-degree relative with a congenital heart defect. Am J Med Genet 1988; 29: 137–142.Google Scholar
11.Patterson, DF, Pexieder, T, Schnarr, WR, Navratil, T, Alaili, R. A single major-gene defect underlying cardiac conotruncal malformations interferes with myocardial growth during embryonic development: Studies in the CTD line of keeshond dogs. Am J Hum Genet 1993; 52: 388–397.Google ScholarPubMed
12.Kogure, K, Miyagawa, S, Ando, M, Takao, A. AV canal defect in a feline species. In: Nora, JJ, Takao, A (eds). Congenital Heart Disease. Causes and Processes. Futura Publishing, New York, 1984, pp 69–77.Google Scholar
13.Whittemore, R, Wells, JA, Castellsague, X. A second-generation study of 427 probands with congenital heart defects and their 837 children. J Am Coll Cardiol 1994; 23: 1459–1467.CrossRefGoogle ScholarPubMed
14.Watkins, H, McKenna, WJ, Thierfelder, L, Suk, HJ, Anan, R, O’Donoghue, A, Spirito, P, Matsumori, A, Moravec, CS, Seidman, JG, Seidman, CE. Mutations in the genes for cardiac troponin T and -tropomyosin in hypertrophic cardiomyopathy. N Engl J Med 1995; 332: 1058–1064.Google Scholar
15.Olson, TM, Michels, W, Lindor, NM, Pastores, GM, Weber, JL, Schaid, DJ, Driscoll, DJ, Feldt, RH, Thibodeau, SN. Autosomal dominant supravalvular aortic stenosis: localization to chromosome 7. Hum Molec Genet 1993; 2: 869–873.Google Scholar
16.Rein, AJJT, Dollberg, S, Gale, R. Genetics of conotruncal malformations: Review of the literature and report of a consanguineous kindred with various conotruncal malformations. Am J Med Genet 1990; 36: 353–355.Google Scholar
17.Wilson, DI, Goodship, JA, Burn, J, Cross, IE, Scambler, PJ. Deletions within chromosome 22qll in familial congenital heart disease. Lancet 1992; 340: 573–575.Google Scholar
18.Digilio, MC, Marino, B, Cicini, MP, Giannotti, A, Formigari, R, Dallapiccola, B. Risk of congenital heart defects in relatives of patients with atrioventricular canal. Am J Dis Child 1993; 147: 1295–1297.Google Scholar
19.Kumar, A, Williams, CA, Victorica, BE. Familial atrioventricular septal defect: possible genetic mechanisms. Br Heart J 1994; 71: 79–81.CrossRefGoogle ScholarPubMed
20.Digilio, MC, Giannotti, A, Marino, B, Obregon, MG, Dallapiccola, B. aDiscrete membranous subaortic stenosis in siblings. Eur J Pediatr 1993; 152: 622.Google Scholar
21.Sletten, LJ, Pierpont, MEM. Familial occurrence of patent ductus arteriosus. Am J Med Genet 1995; 57: 27–30.Google Scholar
22.Dietz, HC, Pyeritz, RE, Hall, BD, Cadle, RG, Hamosh, A, Schwartz, J, Meyers, DA, Francomano, CA. The Marfan syndrome locus: Confirmation of assignment to chromosome 15 and identification of tightly linked markers at 15q15–q21.3. Genomics 1991; 9: 355–361.Google Scholar
23.Sampson, JR, Janssen, LAJ, Sandkuijl, LA, and the Tuberous Sclerosis Collaborative Group. Linkage investigation of three putative tuberous sclerosis determining loci on chromosomes 9q, 11q, and 12q. J Med Genet 1992; 29: 861–866.CrossRefGoogle ScholarPubMed
24.Scambler, PJ, Kelly, D, Lindsay, E, Williamson, R, Goldberg, R, Shprintzen, R, Wilson, DI, Goodship, JA, Cross, IE, Burn, J. Velo-cardio-facial syndrome associated with chromosome 22 deletions encompassing the DiGeorge locus. Lancet 1992; 339: 1138–1139.CrossRefGoogle ScholarPubMed
25.McKusick, VA. Mendelian inheritance in man. A catalog of human genes and genetic disorders. The John Hopkins University Press, Baltimore and London, 1994.Google Scholar
26.Basson, CT, Cowley, GS, Solomon, SD, Weissman, B, Poznanski, AK, Traill, TA, Seidman, JG, Seidman, CE. The clinical and genetic spectrum of the Holt-Oram syndrome (Heart-hand syndrome). N Engl J Med 1994; 330: 885–891.Google Scholar
27.Burch, M, Sharland, M, Shinebourne, E, Smith, G, Patton, M, McKenna, W. Cardiologic abnormalities in Noonan syndrome: phenotypic diagnosis and echocardiographic assessment of 118 patients. J Am Coll Cardiol 1993; 22: 1189–1192.Google Scholar
28.Marino, B, Gagliardi, MG, Digilio, MC, Polletta, B, Grazioli, S, Agostino, D, Giannotti, A, Dallapiccola, B. Noonan syndrome: structural abnormalities of the mitral valve causing subaortic obstruction. Eur J Pediatr 1995 [In press]Google Scholar
29.Jamieson, CR, van, der Burgt I, Brady, AF, van, Reen M, Elsawi, MM, Hoi, F, Jeffery, S, Patton, MA, Mariman, E. Mapping a gene for Noonan syndrome to the long arm of chromosome 12. Nature Genet 1994; 8: 357–360.Google Scholar
30.Hollister, DW, Godfrey, M, Sakai, LY, Pyeritz, RE. Marfan syndrome: immunohistologic abnormalities of the elastin-associated microfibrillar fiber system. N Engl J Med 1990; 323: 152–159.Google Scholar
31.Kanuilainen, K, Pulkkinen, L, Savoilamen, A. Location on chromosome 15 of the gene defect causing Marfan syndrome. N Engl J Med 1990; 323: 935–939.Google Scholar
32.Magenis, RE, Maslen, CL, Smith, L, Allen, L, Sakai, L. Location of the fibrillin (FBN) gene to chromosome 15, band q21.1. Genomics 1991; 11: 346–351.Google Scholar
33.Nijbroek, G, Sood, S, Mclntosh, I, Francomano, CA, Bull, E, Pereira, L, Ramirez, F, Pyeritz, RE, Dietz, HC. Fifteen novel FBN1 mutations causing Marfan syndrome detected by heteroduplex analysis of genomic amplicons. Am J Hum Genet 1995; 57: 8–21.Google Scholar
34.Viljoen, D. Congenital contractural arachnodactyly (Beals syndrome). J Med Genet 1994; 31: 640–643.Google Scholar
35.Collod, G, Babron, MC, Jondeau, , Coulon, M, Weissenbach, J, Dubourg, O, Bourdarias, JP, Bonaiti-PellieCJunien, C, Boileau, C. A second locus for Marfan syndrome maps to chromosome 3p24.2–25. Nature Genet 1994; 8: 264–268.Google Scholar
36.DiSegni, E, Pierpont, MEM, Bass, JL, Kaplinsky, E. Two dimensional echocardiography in detection of endocardial cushiondefect in families. Am JCardiol 1985; 55: 1649–1652.Google Scholar
37.O’Nuallain, S, Hall, JG, Stamm, SJ. Autosomal dominant inheritance of endocardial cushion defect. BDOAS 1977; 13: 143–147.Google Scholar
38.Digilio, MC, Marino, B, Giannotti, A, Dallapiccola, B. Familial atrioventricular septal defect: possible genetic mechanism. Br Heart J 1994; 72: 301.Google Scholar
39.Korenberg, JR, Bradley, C, Disteche, CM. Down syndrome: Molecular mapping of the congenital heart disease and duodenal stenosis. Am J Hum Genet 1992; 50: 294–302.Google Scholar
40.Ferencz, C, Neill, CA, Boughman, JA. Congenital cardiovascular malformations with chromosome abnormalities: an epidemiologic study. J Pediatr 1989; 114: 79–86.Google Scholar
41.Marino, B. Congenital heart disease in patients with Down’s syndrome: anatomic and genetic aspects. Biomed  & Pharmacother 1993; 47: 197–200.Google Scholar
42.Marino, B, Reale, A, Giannotti, A, Digilio, MC, Dallapiccola, B. Nonrandom association of atrioventricular canal and del(8p) syndrome. Am J Med Genet 1992; 42: 424–427.Google Scholar
43.Digilio, MC, Giannotti, A, Marino, B, Dallapiccola, B. Atrioventricular canal and 8psyndrome. Am J Med Genet 1993; 47: 437–438.Google Scholar
44.Cousineau, AJ, Lauer, RM, Pierpont, MEM, Burns, TL, Ardinger, RH, Patil, SR, Sheffield, VC. Linkage analysis of autosomal dominant atrioventricular canal defects: Exclusion of chromosome 21. Hum Genet 1994; 93: 103–108.Google Scholar
45.Wilson, L, Curtis, A, Korenberg, JR, Schipper, RD, Allan, L, Chenevix-Trench, G, Stephenson, A, Goodship, J, Burn, J. A large, dominant pedigree of atrioventricular septal defect (AVSD): exclusion from the Down syndrome critical region on chromosome 21. Am J Hum Genet 1993; 53: 1262–1268.Google Scholar
46.Gennarelli, M, Novelli, G, Digilio, MC, Giannotti, A, Marino, B, Dallapiccola, B. Exclusion of linkage with chromosome 21 in families with recurrence of non-Down’s atrioventricular canal. Hum Genet 1994; 94: 708–710.Google Scholar
47.Amati, F, Mari, A, Mingarelli, R, Gennarelli, M, Digilio, MC, Giannotti, A, Marino, B, Novelli, G, Dallapiccola, B. Two pedigrees of autosomal dominant atrioventricular canal defect (AVCD): Exclusion from the critical region on 8p. Am J Med Genet 1995; 57: 483–488.Google Scholar
48.De, Biase L, Di, Ciommo V, Ballerini, L, Bevilacqua, M, Marcelletti, C, Marino, B. Prevalence of left-sided obstructive lesions in patients with atrioventricular canal without Down syndrome. J Thorac Cardiovasc Surg 1986; 91: 467–472.Google Scholar
49.Marino, B, Vairo, U, Corno, A, Nava, S, Guccione, P, Calabro, R, Marcelletti, C. Atrioventricular canal in Down syndrome. Am J Dis Child 1990; 144: 1120–1122.Google Scholar
50.Carmi, R, Ferencz, C, Boughman, JA. Endocardial cushion defect: Further studies of “isolated” versus “syndromic” occurrence. Am J Med Genet 1992; 43: 569–575.Google Scholar
51.de, la Chapelle A, Herva, R, Koivisto, M, Aula, P. A deletion in chromosome 22 can cause DiGeorge syndrome. Hum Genet 1981; 57: 253–256.Google Scholar
52.Kelley, RI, Zackai, EH, Emanuel, BS, Kistenmacher, M, Greenberg, F, Punnett, HH. The association of the DiGeorge anomalad with partial monosomyofchromosome22. J Pediatr 1982; 101: 197–200.Google Scholar
53.Greenberg, F, Elder, FFB, Haffner, P, Northrup, H, Ledbetter, DH. Cytogenetic findings in a prospective series of patients with DiGeorge anomaly. Hum Genet 1988; 43: 605–611.Google Scholar
54.Dallapiccola, B, Marino, B, Giannotti, A, Valorani, G. DiGeorge anomaly associated with partial deletion of chromosome 22. Report of a case with X/22 translocation and review of the literature. Ann Genet 1989; 32: 92–96.Google ScholarPubMed
55.Wilson, DI, Cross, IE, Goodship, JA, Brown, J, Scambler, PJ, Bain, HH, Taylor, JFN, Walsh, K, Bankier, A, Burn, J, Wolstenholme, J. A prospective cytogenetic study of 36 cases of DiGeorge syndrome. Am J Hum Genet 1992; 51: 957–963.Google Scholar
56.Conley, ME, Beckwith, JB, Mancer, JFK, Tenckhoff, L. The spectrum of the DiGeorge syndrome. J Pediatr 1979; 94: 883–890.Google Scholar
57.Van, Mierop LHS, Kutsche, LM. Cardiovascular anomalies in DiGeorge syndrome and importance of neural crest as a possible pathogenetic factor. Am JCardiol 1986; 58: 133–137.Google Scholar
58.Driscoll, DA, Salvin, J, Sellinger, B, Budarf, ML, McDonaldMcGinn, DM, Zackai, E, Emanuel, BS. Prevalence of 22qll microdeletions in DiGeorge and velocardiofacial syndromes: implications for genetic counselling and prenatal diagnosis. J Med Genet 1993; 30: 813–817.CrossRefGoogle Scholar
59.Burn, J, Takao, A, Wilson, D, Cross, I, Momma, K, Wadey, R, Scambler, P, Goodship, J. Conotruncal anomaly face syndrome is associated with a deletion within chromosome 22ql 1. J Med Genet 1993; 30: 822–824.Google Scholar
60.Stevens, CA, Carey, JC, Shigeoka, AO. DiGeorge anomaly and velocardiofacial syndrome. Pediatrics 1990; 85: 526–530.Google Scholar
61.Lipson, AH, Yuille, D, Angel, M, Thompson, PG, Vandervoord, JG, Beckenham, EJ. Velocardiofacial (Shprintzen) syndrome: an important syndrome for the dysmorphologist to recognise. J Med Genet 1991; 28: 596–604.Google Scholar
62.Goldberg, R, Motzkin, B, Marion, R, Scambler, PJ, Shprintzen, RJ. Velo-cardio-facial syndrome: a review of 120 patients. Am J Med Genet 1993; 45: 313–319.Google Scholar
63.Driscoll, DA, Spinner, NB, Budarf, ML, McDonald-McGinn, DM, Zackai, EH, Goldberg, RB, Shprintzen, RJ, Saal, HM, Zonana, J, Jones, MC, Mascarello, JT, Emanuel, BS. Deletions and microdeletions of 22q 11.2 in velo-cardio-facial syndrome. Am J Med Genet 1992; 44: 261–268.Google Scholar
64.Wilson, DI, Burn, J, Scambler, P, Goodship, J. DiGeorge syndrome: part of CATCH 22. J Med Genet 1993; 30: 852–856.Google Scholar
65.Chow, EWC, Bassett, AS, Weksberg, R, Velo-cardio-facial syndrome and psychotic disorders: Implications for psychiatric genetics. Am J Med Genet 1994; 54: 107–112.Google Scholar
66.Giannotti, A, Digilio, MC, Marino, B, Mingarelli, R, Dallapiccola, B. Cayler cardiofacial syndrome and de122ql 1: Part of the CATCH22 phenotype. Am J Med Genet 1994; 53: 303–304.Google Scholar
67.Nickel, RE, Fillers, DAM, Merkens, M, Magenis, RE, Driscoll, DA, Emanuel, BS, Zonana, J. Velo-cardio-facial syndrome and DiGeorge sequence with meningomyelocele and deletions of the 22ql 1 region. Am J Med Genet 1994; 52: 445–449.CrossRefGoogle Scholar
68.Lipson, A, Emanuel, B, Colley, P, Pagan, K, Driscoll, D. “CATCH 22” sans cardiac anomaly, thymic hypoplasia, cleft palate, and hypocalcaemia: cAtch 22. A common result of 22ql 1 deficiency? J Med Genet 1994; 31: 741.Google Scholar
69.Holder, SE, Winter, RM, Kamath, S, Scambler, PJ. Velocardiofacial syndrome in a mother and daughter: variability of the clinical phenotype. J Med Genet 1993; 30: 825–827.Google Scholar
70.McLean, SD, Saal, HM, Spinner, NB, Emanuel, BS, Driscoll, DA. Velo-cardio-facial syndrome. Intrafamilial variability of the phenotype. Am J Dis Child 1993; 147: 1212–1216.Google Scholar
71.Marmon, LM, Balsara, RK, Chen, R, Dunn, JM. Congenital cardiac anomalies associated with the DiGeorge syndrome: A neonatal experience. Ann Thorac Surg 1984; 38: 146–150.Google Scholar
72.Young, D, Shprintzen, RJ, Goldberg, RB. Cardiac malformations in the velocardiofacial syndrome. Am J Cardiol 1980; 46: 643–648.Google Scholar
73.Melchionda, S, Digilio, MC, Mingarelli, R, Novelli, G, Scambler, P, Marino, B, Dallapiccola, B. Transposition of the great arteries associated with deletion of chromosome 22q 11. Am J Cardiol 1995; 75: 95–98.CrossRefGoogle Scholar
74.Wilson, DI, Goodship, JA, Scambler, PJ, Carey, A, Cross, I, Burn, J. Is monosomy for the DiGeorge locus on chromosome 22 responsible for isolated heart malformations? Am J Hum Genet 1991; 49: 901.Google Scholar
75.Goldmuntz, E, Driscoll, D, Budarf, ML, Zackai, EH, McDonaldMcGinn, DM, Biegel, JA, Emanuel, BS. Microdeletions of chromosomal region 22qll in patients with congenital conotruncal cardiac defects. J Med Genet 1993; 30: 807–812.CrossRefGoogle Scholar
76.Amati, F, Mari, A, Digilio, MC, Mingarelli, R, Marino, B, Giannotti, A, Novelli, G, Dallapiccola, B. 22ql 1 deletions in isolated and syndromic patients with tetralogy of Fallot. Hum Genet 1995; 95: 479–482.Google Scholar
77.Marino, B, Digilio, MC, Grazioli, S, Formigari, R, Mingarelli, R, Giannotti, A, Dallapiccola, B. Tetralogy of Fallot: associated cardiac anomalies in isolated and syndromic patients. Am J Cardiol 1996. [In press]Google Scholar
78.Kirby, ML, Waldo, KL. Role of neural crest in congenital heart disease. Circulation 1990; 82: 332–340.Google Scholar
79.Halford, S, Wadey, R, Roberts, C, Daw, SCM, Whiting, JA, O’Donnell, H, Dunham, I, Bentley, D, Lindsay, E, Baldini, A, Francis, F, Lehrach, H, Williamson, R, Wilson, DI, Goodship, J, Cross, I, Burn, J, Scambler, PJ. Isolation of a putative transcriptional regulator from the region of 22ql 1 deleted in DiGeorge syndrome, Shprintzen syndrome and familial congenital heart disease. Hum Mol Genet 1993; 2: 2099–2107.Google Scholar
80.Wadey, R, Daw, S, Taylor, C, Atif, U, Kamath, S, Halford, S, O’Donnell, H, Wilson, D, Goodship, J, Burn, J, Scambler, P. Isolation of a gene encoding an integral membrane protein from the vicinity of a balanced translocation breakpoint associated with DiGeorge syndrome. Hum Mol Genet 1995; 4: 1027–1033.Google Scholar
81.Demczuk, S, Aledo, R, Zucman, J, Delattre, O, Desmaze, C, Dauphinot, L, Jalbert, P, Rouleau, GA, Thomas, G, Aurias, A. Cloning of a balanced translocation breakpoint in the DiGeorge syndrome critical region and isolation of a novel potential adhesion gene in its vicinity. Hum Mol Genet 1995; 4: 551–558.Google Scholar
82.Budarf, ML, Collins, J, Gong, W, Roe, B, Wang, Z, Bailey, LC, Sellinger, B, Michaud, D, Driscoll, DA, Emanuel, BS. Cloning a balanced translocation associated with DiGeorge syndrome and identification of a disrupted candidate gene. Nature Genet 1995; 10: 269–278.Google Scholar
83.Schmidt, MA, Ensing, GJ, Michels, W, Carter, GA, Hagler, DJ, Feldt, RH. Autosomal dominant supravalvular aortic stenosis: large three-generation family. Am J Med Genet 1989; 32: 384–389.Google Scholar
84.Morris, CA, Loker, J, Ensing, G, Stock, AD. Supravalvular aortic stenosis cosegregates with a familial 6;7 translocation which disrupts the elastin gene. Am J Med Genet 1993; 46: 737–744.Google Scholar
85.Fazio, MJ, Mattei, MG, Passarge, E, Chu, ML, Black, D, Solomon, E, Davidson, JR, Uitto, J. Human elastin gene: new evidence for localization to the long arm of chromosome 7. Am J Hum Genet 1991; 48: 696–703.Google Scholar
86.Curran, ME, Atkinson, DL, Ewart, AK, Morris, CA, Leppert, MF, Keating, MT, The elastin gene is disrupted by a traslocation associated with supravalvular aortic stenosis. Cell 1993; 73: 159–168.Google Scholar
87.Ewart, AK, Morris, CA, Atkinson, D, Jin, W, Sternes, K, Spallone, P, Stock, AD, Leppert, M, Keating, MT. Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Nature Genet 1993; 5: 11–16.Google Scholar
88.Mari, A, Amati, F, Mingarelli, R, Giannotti, A, Sebastio, G, Colloridi, V, Novelli, G, Dallapiccola, B. Analysis of the elastin gene in 60 patients with clinical diagnosis of Williams syndrome. Hum Genet 1995; 96: 444–448.Google Scholar
89.Lowery, MC, Morris, CA, Ewart, A, Brothman, LJ, Zhu, XL, Leonard, CO, Carey, JC, Keating, M, Brothman, AR. Strong correlation of elastin deletions, detected by FISH, with Williams syndrome: Evaluation of 235 patients. Am J Hum Genet 1995; 57: 49–53.Google Scholar