SCIENCE UP THE WORLD 15TH INTERNATIONAL STUDENT CONGRESS OF MEDICAL SCIENCES JUNE 3RD - 6TH 2008

Abstract Mark Mariathas

The Genetic Basis of Hypoplastic Left Heart Syndrome
1M. Mariathas, 1K. Wilkinson, 1C. Spalluto, 1V. Phillips, 1D. Fowler, 1D. I. Wilson 1Division of Human Genetics, University of Southampton, Southampton, England (United Kingdom)

Introduction
Hypoplastic Left Heart Syndrome (HLHS) is a severe congenital heart defect (CHD). It occurs in 1 in 5000 live births and is the most common cause of death in the first week of life. The characteristic morphological features of HLHS are severe by underdevelopment of the left ventricle, aortic valve atresia, and severe narrowing of the aortic arch. Untreated HLHS is lethal. There is significant evidence that genetics plays a role in the aetiology of HLHS.

Most patients with HLHS have normal chromosomes using standard light microscopy. For a chromosomal rear­rangement to be detected using light microscopy, at least 4 million base pairs must be deleted or duplicated. It is possible that there are smaller deletions or duplications in patients with HLHS that are undetected by light microscopy. A new technology has been developed that improves the resolution termed Microarray-Comparative Genomic Hybridization (Microarray-CGH).

Can submicroscopic chromosomal rearrangements cause HLH?

Method and Materials
Informed consent and ethical approval was obtained for this study. Twenty patients with HLHS were recruited to the study. DNA was collected from these patients. Chromosome analysis was performed on these patients using standard light microscopy. All twenty patients had normal chromosomes. These twenty patients were then inves­tigated using Microarray-CGH. Microarray-CGH microscope slides were fabricated in house using DNA from targeted genetic regions critical for cardiac development. All results were confirmed via a second independent method. The second independent method used was Fluorescent In Situ Hybridization (FISH).

Results
This study confirmed that 1q42 and 11q25 are critical regions in the development of HLHS. The critical region on 1q42 was narrowed down to 6-Mb. On 11q25 the critical region was narrowed down to 8-Mb.

Conclusion
These results have identified two critical chromosomal regions involved in HLHS. The genes in these regions must now be investigated to find a cause for HLHS.

 Keyword(s): Genetics, Hypoplastic Left Heart Syndrome, Pediatric Cardiology