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ABCA4-Related Retinopathies in Lebanon: a novel mutation and significant heterogeneity

Ibrahim, M.; Jaffal, L.; Assi, A.; Helou, C.; El Shamieh, S.

2023-11-10 genetic and genomic medicine
10.1101/2023.11.09.23298241 medRxiv
Show abstract

Mutations in ATP-binding cassette transporter type A4 (ABCA4) have been linked to several forms of inherited retinal diseases (IRDs) besides the classically defined Stargardt disease (STGD), known as ABCA4 retinopathies. ABCA4 is a sizeable locus harboring 50 exons; thus, its analysis has revealed a rich area of genetic information comprising at least 1,200 disease-causing mutations of varied severity and types. Due to the clinical and genetic heterogeneity, diagnosing ABCA4 retinopathies is challenging. To date, no ABCA4-retinopathy has been detected in Lebanon. Using next-generation sequencing, we sought to pinpoint the mutation spectrum in seven families with different forms of IRDs: STGD, rod-cone and cone-rod dystrophies (RCD and CRD, respectively). Eight ABCA4 mutations were found, including one novel; c.4330G>C; p.(Trp1408Cys). Three families were diagnosed with CRD, two with STGD, and two others with RCD. In conclusion, our study revealed a novel ABCA4 mutation and showed significant genotypic and phenotypic heterogeneity in Lebanon.

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