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This abstract is assigned to session Poster session in O'Bistro

Title

Cryptic chromosomal deletions and duplications as a cause of congenital eye malformations

Purpose	Congenital ocular malformations (COM) are a frequent cause of childhood blindness. Mutations in a variety of genes known to be involved in the development of the eye can underlie COM. However, a large number of patients remains without a molecular diagnosis. Large chromosomal aberrations such as trisomies 13 and 18 are known to cause a variety of eye anomalies, such as microphtalmia, anophtalmia and coloboma. Such large aberrations are cytogenetically detectable using metaphase chromosome spreads. The purpose of the current study was to investigate the role of smaller chromosomal deletions and duplications in the etiology of COM.
Methods	We applied Agilent 244K oligoarray copy number profiling platform for the analysis of patients with various idiopathic COM. The resolution of this platform is 100-fold higher than what can be achieved using metaphase spreads.
Results	We analyzed 38 patients and identified causal deletions in 5 patients (13%). Most of these deletions affected known genes (OTX2, PAX6, FOXC1 and COH1) but were found in patients with atypical presentations, thus broadening the phenotypic spectrum associated with mutations in these genes. Deletions were not enriched in any class of COM.
Conclusion	Our findings clearly demonstrate that hitherto cryptic deletions and duplications contribute to the etiology of a variety of ocular developmental defects, and that diagnostic methods allowing high resolution analysis of chromosomal copy number changes improve the diagnosis of the patients with congenital eye anomalies.

Authors 1

Last name	BALIKOVA
Initials	I
Department	Departement of Ophthalmology CHU St Pierre
City	Brussels

Authors 2

Last name	DE RAVEL
Initials	T
Department	Centre for Human Genetics
City	Leuven

Authors 3

Last name	Ayuso
Initials	C
Department	Fundación Jyménes Díaz
City	Madrid, Spain

Authors 4

Last name	Casteels
Initials	I
Department	Department of Ophthalmology
City	Leuven

Authors 5

Last name	Fryns
Initials	JP
Department	Centre for Human Genetics
City	Leuven

Authors 6

Last name	Vermeesch
Initials	JR
Department	Centre for Human Genetics
City	Leuven