Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-27T09:08:08.107Z Has data issue: false hasContentIssue false
  • English
  • Français

New trends in chromosomal investigation in children with cardiovascular malformations

Published online by Cambridge University Press:  21 January 2005

Ruth Schellberg ,
Gesa Schwanitz ,
Lutz Grävinghoff ,
Rolf Kallenberg ,
Detlef Trost ,
Ruth Raff  and
Walter Wiebe
Ruth Schellberg
Affiliation:
Institute of Human Genetics, University Bonn, Germany
Gesa Schwanitz
Affiliation:
Institute of Human Genetics, University Bonn, Germany
Lutz Grävinghoff
Affiliation:
Asklepios Clinic, Deutsches Kinderherzzentrum, Sankt Augustin, Germany
Rolf Kallenberg
Affiliation:
Asklepios Clinic, Deutsches Kinderherzzentrum, Sankt Augustin, Germany
Detlef Trost
Affiliation:
Institute of Human Genetics, University Bonn, Germany
Ruth Raff
Affiliation:
Institute of Human Genetics, University Bonn, Germany
Walter Wiebe
Affiliation:
Asklepios Clinic, Deutsches Kinderherzzentrum, Sankt Augustin, Germany
Get access Rights & Permissions [Opens in a new window]

Abstract

We investigated a group of 376 children, seen over a period of 7 years with different types of congenital cardiovascular defects, to assess the presence of chromosomal aberrations. The diagnostic approach, achieved in 3 consecutive steps, revealed conventional chromosomal aberrations in 30 of the patients (8%) excluding trisomies 13, 18, 21. Fluorescence in situ hybridisation for microdeletions showed 51 microdeletions (15%), with 43 patients having deletions of 22q11.2, 7 patients with deletion of 7q11.23, and 1 patient with deletion of 4p16.3. In 23 patients with additional clinical abnormalities, we carried out a subtelomeric screening. This revealed, in two cases (9%), different subtelomeric aberrations, namely deletions of 1p and of 1q. Thus, subtelomeric screening proved to be a very valuable as a new diagnostic approach. Our approach to genetic investigation in three phases makes it possible to detect a high rate of pathologic karyotypes in patients with congenital cardiovascular malformations, thus guaranteeing more effective genetic counselling of the families, and a more precise prognosis for the patient.

Keywords

Chromosomal aberrationsmicrodeletionssubtelomeric aberrationsfluorescence in situ hybridisation
Type
Original Article
Information
Cardiology in the Young , Volume 14 , Issue 6 , December 2004 , pp. 622 - 629
Copyright
© 2004 Cambridge University Press

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

Nora JJ, Berg K, Nora AH. Cardiovascular Diseases. Oxford University Press, 1991.
Baumer A, Dutly F, Balmer D, et al. High level of unequal meiotic crossovers at the origin of the 22q11.2 and 7q11.23 deletions. Hum Mol Genetics 1998; 7: 887–894.Google Scholar
Knight SJ, Regan R, Nicod A, et al. Subtle chromosomal rearrangements in children with unexplained mental retardation. Lancet 1999; 354: 1676–1681.Google Scholar
Schwanitz G, Zerres K, Gembruch U, Bald R, Gamerdinger F, Hansmann M. Prenatal detection of heart defects as an indication for chromosomal analysis. Ann Génét 2000; 33: 79–83.Google Scholar
Ferencz C, Neill CA, Boughman JA, Rubin JD, Brenner JI, Perry LW. Congenital cardiovascular malformations associated with chromosome abnormalities: an epidemiologic study. J Pediatr 1989; 114: 79–86.Google Scholar
Hoffman JI, Christianson R. Congenital heart disease in a cohort of 19,502 births with long-term follow-up. Am J Cardiol 1978; 42: 641–647.Google Scholar
van Karnebeek CD, Hennekam RC. Associations between chromosomal anomalies and congenital heart defects: a database search. Am J Med Genet 1999; 84: 158–166.Google Scholar
Kaiser-Rogers K, Rao K. Structural chromosome rearrangements. In: Gersen S, Keagle M (eds). Principles of Clinical Cytogenetics. Humana Press Inc., Totowa, NJ, 1999, pp 198–228.
Raff R, Schwanitz G. Fluorescence in situ hybridization: general principles and clinical application with special emphasis to interphase diagnostics. Int J Hum Genet 2001; 1: 65–75.Google Scholar
Fokstuen S, Arbenz U, Artan S, et al. 22q11.2 deletions in a series of patients with non-selective congenital heart defects: incidence, type of defects and parental origin. Clin Genet 1998; 53: 63–69.Google Scholar
Marino B, Digilio MC, Toscano A, Gianotti A, Dallapiccola B. Congenital heart defects in patients with DiGeorge/velocardiofacial syndrome and del 22q11.2. Genet Couns 1999; 10: 25–33.Google Scholar
Mehraein Y, Wippermann CF, Michel-Behnke I, et al. Microdeletion 22q11 in complex cardiovascular malformations. Human Genet 1997; 99: 433–442.Google Scholar
Takahashi K, Kido S, Hoshino K, Ogawa K, Ohashi H, Fukushima Y. Frequency of a 22q11 deletion in patients with conotruncal cardiac malformations: a prospective study. Eur J Pediatr 1995; 154: 878–881.Google Scholar
Burn J, Wilson DI, Cross I, Atif U, Scambler P, Takao A. The significance of 22q11 deletion. In: Clark EB, Takao A (eds). Developmental Mechanisms of Heart Disease. Futura Publ, Armonk-New York, 1995, pp 559–567.
Chung MY, Lu JH, Chien HP, Hwang B. Chromosome 22q11 microdeletion in cardiovascular heart defects: clinical presentation, parental origin and de novo mutations. Int J Mol Med 2001; 7: 501–505.Google Scholar
Trost D, Wiebe W, Uhlhaas S, Schwindt P, Schwanitz G. Investigation of meiotic rearrangements in DGS/VCFS patients with a microdeletion 22q11.2. J Med Genet 2000; 37: 452–454.Google Scholar
Bayés M, Magano LF, Rivera N, Flores R, Pérez Jurado LA. Mutational mechanisms of Williams-Beuren syndrome deletions. Am J Hum Genet 2003; 73: 131–151.Google Scholar
Saccone S, De Sario A, Della Valle G, Bernardi G. The highest gene concentrations in the human genome are telomeric bands of metaphase chromosomes. Proc Natl Sci USA 1992; 89: 4913–4917.Google Scholar
De Vries BB, Winter R, Schinzel A, van Ravenswaaij-Arts C. Telomeres: a diagnosis at the end of the chromosomes. J Med Genet 2003; 40: 385–398.Google Scholar
Xu J, Chen Z. Advances in molecular cytogenetics for the evaluation of mental retardation. Am J Med Genet 2003; 117C: 15–24.Google Scholar