Date of Award
16-12-2024
Document Type
Thesis
School
School of Chemical & Biotechnology
Programme
Ph.D.-Doctoral of Philosophy
First Advisor
Dr.S.Sripriya
Second Advisor
Dr.Suma Mohan
Keywords
Next Generation Sequencing, Genetic Etiology, Syndromic Blindness, Retinitis Pigmentosa, Human Genetics
Abstract
India is one of the largest populations in the world and is estimated to have a high prevalence of Retinitis Pigmentosa (RP). RP is clinically and genetically heterogenous, characterized initially as night blindness, leading to complete vision loss due to retinal degeneration. RP can occur in non-syndromic or syndromic forms, affecting other organs as observed in Bardet Biedl Syndrome (BBS) and Usher syndrome (USH).
BBS is characterized by RP, polydactyly, obesity, renal anomalies and learning difficulties. USH is characterized by RP and sensorineural hearing loss (SNHL), with variable presence of vestibular dysfunction. Nextgeneration sequencing (NGS) has become a cost-effective technology for rapid and accurate data generation and analysis in genetic studies.
In this study, NGS was used to screen patients clinically diagnosed with syndromic RP and Leber Congenital Amaurosis (LCA)/Severe Early Congenital Onset Retinal Degeneration (SECORD)) after detailed ophthalmic examinations and documentation of extraocular features through a proforma and questionnaire.
A total of 207 (N=108 BBS, N=90 USH and N=9 retrospective SECORD) patients were analysed for genetic etiology; pathogenic variations were identified in 85% of BBS and 84% of USH in known genes; N= 48 in BBS and N=36 in USH were novel variations. Eleven patients showed variations in other IRD and ciliary genes (3 BBS and 8 USH); noncandidate gene variations were identified in 5 BBS and 3 USH patients through whole exome sequencing; however, the disease causal role of these variations deems further clinical evaluation and correlation.
Genetic alterations were not identified in 9% and 6% of BBS and USH patients respectively. The study also revealed the potential of NGS in re-diagnosis of syndromic forms of LCA/SECORD in patients who were initially diagnosed as isolated RP cases. The study has expanded the knowledge on genetic spectrum of BBS and USH patients from India and is the only available report from the country.
This study gains momentum in the context of emerging gene based therapeutic interventions and also validates the need for early molecular diagnosis, which will aid in the (i) management of syndromic conditions (ii) confirmation of disease pathogenesis through differential diagnosis based on the genes identified.
Recommended Citation
G, Harshavardhini Ms, "Next Generation Sequencing based Profiling of Genes in Patients with Syndromic forms of Retinitis Pigmentosa" (2024). Theses and Dissertations. 35.
https://knowledgeconnect.sastra.edu/theses/35