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TitelThe power of homozygosity mapping-guided whole exome sequencing in a Saudi LCA population.
Abstract Nr.1055
DoelLeber 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).
MethodesOur approach consisted of homozygosity mapping followed by targeted next generation sequencing (NGS) or Sanger sequencing, combined or not with whole exome sequencing (WES).
ResultatenOverall, 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).
ConclusieThe 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.
BelangenverstrengelingNee
Auteur 1
NaamALMOALLEM
InitialenB
InstituutCtr.for Med.Genetics,Ghent University
StadGhent
Auteur 2
NaamVan Schil
InitialenK
InstituutCtr.for Med.Genetics,Ghent University
StadGhent
Auteur 3
NaamJeddawi
InitialenL
InstituutDhahran Eye Specialist Hospital
StadDhahran
Auteur 4
NaamRosseel
InitialenT
InstituutCtr.for Med.Genetics,Ghent University
StadGhent
Auteur 5
NaamCoppieters
InitialenF
InstituutCtr.for Med.Genetics,Ghent University
StadGhent
Auteur 6
NaamDe Baere
InitialenE
InstituutCtr.for Med.Genetics,Ghent University
StadGhent
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