THE BELGIAN OPHTHALMIC ASSOCIATIONS
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| Titre | The power of homozygosity mapping-guided whole exome sequencing in a Saudi LCA population. |
| Abstract Nr. | 1055 |
| But | 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). |
| Méthodes | Our approach consisted of homozygosity mapping followed by targeted next generation sequencing (NGS) or Sanger sequencing, combined or not with whole exome sequencing (WES). |
| Résultats | 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. |
| Conflit d'intérêt | Non |
Auteur 1
| Nom | ALMOALLEM |
| Initiales | B |
| Institut | Ctr.for Med.Genetics,Ghent University |
| Ville | Ghent |
Auteur 2
| Nom | Van Schil |
| Initiales | K |
| Institut | Ctr.for Med.Genetics,Ghent University |
| Ville | Ghent |
Auteur 3
| Nom | Jeddawi |
| Initiales | L |
| Institut | Dhahran Eye Specialist Hospital |
| Ville | Dhahran |
Auteur 4
| Nom | Rosseel |
| Initiales | T |
| Institut | Ctr.for Med.Genetics,Ghent University |
| Ville | Ghent |
Auteur 5
| Nom | Coppieters |
| Initiales | F |
| Institut | Ctr.for Med.Genetics,Ghent University |
| Ville | Ghent |
Auteur 6
| Nom | De Baere |
| Initiales | E |
| Institut | Ctr.for Med.Genetics,Ghent University |
| Ville | Ghent |