PT  - JOURNAL ARTICLE
AU  - Abdallah, Mohammed O.E.
AU  - Koko, Mahmoud E.
AU  - Faisal, Shima
AU  - Newport, Melanie J.
AU  - Ibrahim, Muntaser E.
TI  - Recurrent <em>AIPL1</em> c.487C>T truncating variant in Leber Congenital Amaurosis: Support of pathogenicity and regional implications
AID  - 10.1101/290650
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 290650
4099  - http://biorxiv.org/content/early/2018/03/28/290650.short
4100  - http://biorxiv.org/content/early/2018/03/28/290650.full
AB  - Background Leber Congenital Amaurosis (LCA) is a clinically and genetically heterogeneous inherited retinal dystrophy characterized by early onset visual impairment caused by mutations in not less than 17 genes. AIPL1 mutations cause LCA type 4, comprising approximately 7% of LCA worldwide. The importance of establishing a genetic diagnosis lies in the promise of gene therapy demonstrated in mouse models.Results we genetically investigated a consanguineous Sudanese family with Leber Congenital Amaurosis. Eight members of the family were affected. Using whole exome sequencing in two siblings and their healthy mother, both inheritance-based and phenotype-based prioritization strategies converged to identify a truncating variant (rs62637009) in AIPL1, consistent with a diagnosis of LCA type 4. AIPL1 c.487C>T is an ultra-rare cause of LCA4 that was seen previously in homozygous state in a single Palestinian family. This recurrent variant seems to have a regional importance with a likely founder effect.Conclusions This report adds evidence to the pathogenicity of AIPL1 c.487C>T meriting its conclusive annotation as a recurrent pathogenic variant. This variant is particularly relevant to the middle-eastern and northeast African regions.