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Title	The power of homozygosity mapping-guided whole exome sequencing in a Saudi LCA population.
Abstract Nr.	1055

Purpose	Leber congenital amaurosis is the most severe autosomal recessive retinal dystrophy (RD) accounting for 5% of childhood blindness. Thus far 70% of LCA cases have been explained by 21 known genes. Here, we aim to identify the genetic cause in 15 Saudi-Arabian families with a total of 20 probands (8 females and 12 males), and age of 2-9 years, displaying severe vision impairment, nystagmus, sluggish or near-absent pupillary responses, oculodigital sign, and severely reduced or extinguished electroretinogram (ERG).
Methods	Our approach consisted of homozygosity mapping followed by targeted next generation sequencing (NGS) or Sanger sequencing, combined or not with whole exome sequencing (WES).
Results	Overall, we identified 13 putative pathogenic mutations in 10 known IRD genes in 14/15 (93.3%) of the studied families, six of which are novel. Eight were known LCA genes: CRB1 (3/15,20%), RPGRIP1 (2/15,13.3%), SPATA7 (2/15,13.3 %) and MERTK, RDH12, CABP4, CEP290 (1/15, 6.7% for the latter four).Two genes are known in other forms of IRD (1/15, 6.7% for each): ATF6 with recessive achromatopsia and ALMS1 with Alström syndrome. The recurrent RPGRIP1 mutation c.1007delA p.(Glu370Asnfs*5) was consistent with a potential founder effect in the Saudi population (Khan et al. 2014).
Conclusion	The power of homozygosity mapping-guided WES revealed pathogenic mutations in 93.3% of the studied families. This might offer therapeutic perspectives beside the diagnostic-prognostic values and reproductive options.
Conflict of interest	No

Authors 1

Last name	ALMOALLEM
Initials	B
Department	Ctr.for Med.Genetics,Ghent University
City	Ghent

Authors 2

Last name	Van Schil
Initials	K
Department	Ctr.for Med.Genetics,Ghent University
City	Ghent

Authors 3

Last name	Jeddawi
Initials	L
Department	Dhahran Eye Specialist Hospital
City	Dhahran

Authors 4

Last name	Rosseel
Initials	T
Department	Ctr.for Med.Genetics,Ghent University
City	Ghent

Authors 5

Last name	Coppieters
Initials	F
Department	Ctr.for Med.Genetics,Ghent University
City	Ghent

Authors 6

Last name	De Baere
Initials	E
Department	Ctr.for Med.Genetics,Ghent University
City	Ghent