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Familial atrial septal defect in the oval fossa with progressive prolongation of the atrioventricular conduction caused by mutations in the NKX2.5 gene

Published online by Cambridge University Press:  02 December 2008

Per G. Bjørnstad  and
Trond P. Leren
Per G. Bjørnstad*
Affiliation:
Dept of Paediatric Cardiology and, Rikshospitalet University Hospital, Oslo, Norway
Trond P. Leren
Affiliation:
Dept of Medical Genetics, Rikshospitalet University Hospital, Oslo, Norway
*
Correspondence to: Per G. Bjørnstad, MD. Ph.D., Paediatric Cardiology, Rikshospitalet University Hospital, N-0027 Oslo, Norway. Tel/Fax: +47 2 232 2547; E-mail: perbjo@broadpark.no
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Abstract

Objective

To search for a genetic basis in a family with autosomal dominantly inherited atrial septal defect in combination with increasing conduction anomalies.

Design

We searched for mutations in the NKX2.5 gene by sequencing of desoxyribonucleic acid in a previously investigated family.

Patients

All family members were included if they, after informed consent, had decided to participate in the genetic testing. A blood sample was sent from local doctors for analysis of potential mutations. Patients with cardiac anomalies were examined in our hospital. For those family members without cardiac anomalies, we relied on local information.

Results

We identified the mutation Q149X in the NKX2.5 gene on chromosome 5q35 in all patients with atrial septal defect and disturbances of atrioventricular conduction. No family member without an atrial septal defect possessed the mutation, including a member with transposed arterial trunks.

Conclusion

We have identified a mutation in the NKX2.5 gene responsible for autosomal dominantly inherited atrial septal defect in the oval fossa combined with disturbances of atrioventricular conduction in 7 patients spanning 4 generations.

Keywords

Congenital heart diseasegeneticsfamilial occurrencedominant inheritance
Type
Original Article
Information
Cardiology in the Young , Volume 19 , Issue 1 , February 2009 , pp. 40 - 44
Copyright
Copyright © Cambridge University Press 2008

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References

1. Ehlers, K, Engle, MA. Familial congenital heart disease. I. Genetic and environmental factors. Circulation 1966; 34: 503–516.CrossRefGoogle ScholarPubMed
2. Gill, HK, Splitt, M, Sharland, GK, Simpson, JM. Patterns of recurrence of congenital heart disease: an analysis of 6,640 consecutive pregnancies evaluated by detailed fetal echocardiography. J Am Coll Cardiol 2003; 42: 923–929.CrossRefGoogle Scholar
3. Zetterqvist, P, Turesson, I, Johansson, BW, Laurell, S, Ohlsson, NM. Dominant mode of inheritance in atrial septal defect. Clin Genet 1971; 2: 78–86.CrossRefGoogle ScholarPubMed
4. Kahler, R, Braunwald, E, Plauth, W, Morrow, AG. Familial occurrence of atrial septal defect with A-V conduction abnormalities; supravalvular aortic and pulmonic stenosis; and ventricular septal defect. Am J Med 1966; 40: 384–399.CrossRefGoogle Scholar
5. Emanuel, R, O’Brien, K, Somerville, J, Jefferson, K, Hegde, M. Association of secundum atrial septal defect with abnormalities of atrioventricular conduction or left axis deviation. Genetic study of 10 families. Br Heart J 1975; 37: 1085–1092.CrossRefGoogle ScholarPubMed
6. Bjørnstad, PG. Secundum type atrial septal defect with prolonged PR interval and autosomal dominant mode of inheritance. Br Heart J 1974; 36: 1149–1154.CrossRefGoogle ScholarPubMed
7. McElhinney, DB, Geiger, E, Blinder, J, Benson, DW, Goldmuntz, E. NKX2.5 mutations in patients with congenital heart disease. J Am Coll Cardiol 2003; 42: 1650–1655.CrossRefGoogle ScholarPubMed
8. Benson, DW, Silberbach, GM, Kavanaugh-McHugh, A, et al. Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways. J Clin Invest 1999; 104: 1567–1573.CrossRefGoogle ScholarPubMed
9. Schott, JJ, Benson, DW, Basson, CT, et al. Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science 1998; 281 (5373): 108–111.CrossRefGoogle ScholarPubMed
10. Ikeda, Y, Hiroi, Y, Hosoda, T, et al. Novel point mutation in the cardiac transcription factor CSX/NKX2.5 associated with congenital heart disease. Circ J 2002; 66: 561–563.CrossRefGoogle ScholarPubMed
11. Kasahara, H, Lee, B, Schott, JJ, et al. Loss of function and inhibitory effects of human CSX/NKX2.5 homeoprotein mutations associated with congenital heart disease. J Clin Invest 2000; 106: 299–308.CrossRefGoogle ScholarPubMed
12. Hosoda, T, Komuro, I, Shiojima, I, et al. Familial atrial septal defect and atrioventricular conduction disturbance associated with a point mutation in the cardiac homeobox gene CSX/NKX2-5 in a Japanese patient. Jap Circ J 1999; 63: 246–425.CrossRefGoogle Scholar
13. Hirayama-Yamada, K, Kamisago, M, Akimoto, K, et al. Phenotypes with GATA4 or NKX2.5 mutations in familial atrial septal defect. Am J Med Genet PartA 2005; 135: 47–52.CrossRefGoogle ScholarPubMed
14. Konig, K, Will, JC, Berger, F, Muller, D, Benson, DW. Familial congenital heart disease, progressive atrioventricular block and the cardiac homeobox transcription factor gene NKX2.5: identification of a novel mutation. Clin Res Cardiol 2006; 95: 499–503.CrossRefGoogle ScholarPubMed