Ramesh Reddy
Ramesh Reddy
McGill University
Poster Session

Poster Session B

Monday, 20 April, 2015 - 19:00
Poster Number: 
52

Molecular Genetics of the Usher Syndrome in Lebanon: Identification of 11 Novel Protein-truncating Mutations by Whole Exome Sequencing

Ramesh Reddy1, Somayyeh Fahiminiya2, Elie El Zir3, Ahmad Mansour4, Andre Megarbane5, Jacek Majewski2, Rima Slim1

1. Departments of Human Genetics and Obstetrics-Gynecology, McGill University Health Centre, Montreal, Canada; 2. McGill University and Genome Quebec Innovation Centre and Department of Human Genetics; 3. Department of Otorhinolaryngology, Hôpital Sacré-Coeur, Baabda, Lebanon; 4. Department of Ophthalmology, American University of Beirut, Lebanon; 5. Unité de génétique médicale, Faculté de médecine, Université Saint Joseph, Beirut, Lebanon

Background: Usher syndrome (USH) is a genetically heterogeneous condition with ten disease-causing genes. The spectrum of genes and mutations causing USH in the Lebanese and Middle Eastern populations has not been described. Consequently, diagnostic approaches designed to screen for previously reported mutations were unlikely to identify the mutations in 11 unrelated families, eight of Lebanese and three of Middle Eastern origins. In addition, six of the ten USH genes consist of more than 20 exons, each, which made mutational analysis by Sanger sequencing tedious and costly.

Objective: The study was aimed at the identification of USH causing genes and mutations in 11 unrelated families with USH type I or II.

Methodology and Results: Whole exome sequencing followed by expanded familial validation by Sanger sequencing was performed on the 11 unrelated families. We identified disease-causing mutations in all the analyzed patients in four USH genes, MYO7A, USH2A, GPR98 and CDH23. Eleven of the mutations were novel and protein truncating, including a complex rearrangement in GPR98.

Conclusion: Our data highlight the genetic diversity of Usher syndrome in the Lebanese population and the time and cost-effectiveness of whole exome sequencing approach for mutation analysis of genetically heterogeneous conditions caused by large genes. Identification of 11 novel causative mutations for USH in Lebanon will aid as a first screen of diagnosis for USH patients from this population.