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Identifier

000463850

Title

Analysis of whole exome sequencing data of patients with neurological and renal dosorders

Alternative Title

Ανάλυση δεδομένων αλληλούχισης ολικού εξώματος σε ασθενείς με νευρολογικές και νεφρολογικές παθήσεις

Author

Δράκος, Μηνάς Χρυσοβαλάντης

Thesis advisor

Ζαγανάς, Ιωάννης

Reviewer

Μήτσιας, Παναγιώτης
Στυλιανού, Κωνσταντίνος

Abstract

Today, more than 10,000 rare diseases affect over 300 million individuals worldwide, with 30 million in Europe. Unfortunately, even with a diagnosis established, the average time for diagnosis is 5 to 6 years. Importantly, Next Generation Sequencing (NGS) has transformed the diagnostic landscape, facilitating earlier and more accurate detection of rare diseases. Reanalyzing NGS data in patients with undiagnosed Mendelian (monogenic) disorders is strongly recommended, as it typically leads to an overall yield of 10%, enabling the diagnosis of a significant number of previously undiagnosed patients. The aim of this study was to re-analyze NGS data of patients with rare or undiagnosed diseases for which the molecular cause has not been established. Specifically, we re-analyzed whole-exome sequencing (WES) data from 300 patients with rare and undiagnosed diseases using the RD‐Connect Genome‐Phenome Analysis Platform (GPAP). The cohort, all Caucasians living in Greece, exhibited heterogeneous clinical presentations, primarily within the neurological and developmental abnormality spectrum. Out of 300 patients, 82 received a positive genetic diagnosis, representing a diagnostic yield of 27.7%. Furthermore, we identified 25 previously unreported disease- causing variants and 5 variants associated with the disease that had not been implicated until now. Our efforts resulted in genetically diagnosing 82 patients with rare diseases who were previously undiagnosed. We unveiled 25 novel disease-causing variants and associated 5 known variants with a specific disease for the first time. Two exceptionally rare syndromes were also identified. Specifically, Verheij and White-Sutton syndromes, conditions with only 56 patients and 80 cases described in the literature as of the time of writing.

Language

English

Subject

Neurology

Next generation sequencing

Precision medicine

Αλληλούχηση επόμενης γενιάς

Γενετική

Γονιδιωματική

Νευρολογία

Issue date

2024-04-17