Hereditary spinocerebellar degeneration in Sudanadmin
Hereditary spinocerebellar degeneration in Sudan: maximizing the diagnostic yield through data revisiting
Ashraf Y. O. Mohamed1,4,5, Inaam N. Mohammed1, Ahlam A. A. Hamed1, Maha A. Elseed1, Mahmoud E. Koko2, Rayan A. Siddig1, Mustafa A. Salih, Alexis Brice4,6, Liena E. O. Elsayed1*, Ammar E. Ahmed1*, and Giovanni Stevanin4,5,6.
*Correspondence: Professor Ammar E. Ahmed and Dr.Liena Elbaghir Omer Elsayed, Faculty of Medicine , University of Khartoum, Qasr Street,11111 Khartoum, Sudan.
1Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
2Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Germany
3Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
4Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR7225, Sorbonne Universités, UPMC Université Paris VI UMR_S1127, 75013 Paris, France.
5Ecole Pratique des Hautes Etudes, EPHE, PSL université, 75013 Paris, France.
6APHP Pitié-Salpêtrière Hospital, Department of genetics, 75013 Paris, France.
Background: The post human genome project era has been characterized by a spurt of biological information shifting the quest towards making sense out of biological data rather than data generation. Hereditary degenerative spinocerebellar disorders (SCD) are of the most common inherited (monogenic) neurological diseases with a wide range of genotypic and phenotypic characteristics. In a previous study, we succeeded in identifying new genes, new mutations and novel SCD genotype phenotype correlations using whole exome sequencing (WES) with an overall success rate of 50% (seven out of 14 families).
Methods: Reanalysis of next generation sequencing data on seven Sudanese families with SCD. In a previous study no genetic diagnosis had been reached in these families. Reanalysis was coupled to revisiting clinical phenotypes, models of inheritance and study approaches.
Results: Genetic diagnosis was reached in five families. Three families had novel mutations in known SCD genes. One family had novel mutation in a gene only recently identified to be associated with inherited neurological conditions. One family had a new gene not previously linked to monogenic diseases in humans. We were able to increase our overall success rate on WES analysis to 86% (12 out of 14 families).
Conclusion: Re-evaluation of genotypic and phenotypic data on undiagnosed individuals coupled to adoption of new analysis approaches and utilization of new technical advances can maximize the yield of WES analysis.