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This abstract is assigned to session OB Free papers: Medical retina

Title	FRO: Identification of the causal gene in retinal dystrophies using homozygosity mapping
Abstract Nr.	245

Purpose	Inherited retinal dystrophies are characterized by extreme locus heterogeneity. In the case of Leber Congenital Amaurosis (LCA) and autosomal recessive retinitis pigmentosa (ARRP), the known disease genes account for only 50-70% of all cases. The goal of this study was to use homozygosity mapping in patients with consanguineous parents; not only to identify known disease genes underlying the phenotype, but also to find new disease loci for retinal dystrophies.
Methods	Genomewide homozygosity mapping was performed in 12 isolated probands and 9 affected individuals from 4 families (Affymetrix GeneChip 250K). In the largest homozygous regions, candidate genes were selected and screened using direct sequencing of the total coding region and intron-exon boundaries.
Results	In 6 isolated probands, mutations were identified in a known gene located in the largest homozygous region (RDH12, NPHP5, USH2A and TMEM126A). Moreover, RDH12 was identified as the causal gene in a family with early-onset RP. In the remaining patients, candidate gene screening is ongoing. In addition, no known disease genes were located in the largest homozygous regions in a family with LCA, suggesting the involvement of a novel disease gene.
Conclusion	Homozygosity mapping proved to be a powerful tool for the identification of the causal gene in consanguineous families. In addition, this technique allowed the localization of regions containing a novel disease gene for LCA.

Author 1

Last name	COPPIETERS
Initials	F
Department	Center for Medical Genetics, Ghent University Hospital
City	Ghent

Author 2

Last name	Lefever
Initials	S
Department	Center for Medical Genetics, Ghent University Hospital
City	Ghent

Author 3

Last name	Meire
Initials	F
Department	HUDERF, Hopital Des Enfants Reine Fabiola
City	Brussels

Author 4

Last name	Leroy
Initials	BP
Department	Center for Medical Genetics & Department of Ophthalmology, Ghent University Hospital
City	Ghent

Author 5

Last name	De Baere
Initials	E
Department	Center for Medical Genetics, Ghent University Hospital
City	Ghent