Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.753988
Title: Defining the genetic causes of neurodevelopmental disorders in the Amish
Author: Maroofian, Reza
ISNI:       0000 0004 7427 053X
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2018
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Abstract:
Neurodevelopmental disorders (NDDs) are defined as highly prevalent and debilitating paediatric neurological conditions caused by impairments in brain growth and development. A major contribution to our understanding in this field has been made through the study of monogenic disorders, which are individually rare, but which occur at higher frequencies in genetically isolated populations. This PhD project forms part of a long running research program called ‘Windows of Hope’, which aims to investigate the genetic causes of NDDs in Amish families to aid scientific understanding of these diseases, to provide diagnostic, management and treatment benefits for families. Families with individuals affected by undiagnosed forms of NDD were investigated using whole genome SNP genotyping to map candidate gene loci, identify structural chromosomes and copy number variations. Using whole exome sequencing to identify known and new candidate gene mutations with follow-up sequencing and functional studies. These studies defined a wide range of known genetic causes of NDDs, and identified disorders involving rare genomic chromosomal rearrangements, providing diagnoses for several families. In addition, these studies contributed to the definition of two new autosomal recessive forms of NDDs (B4GALNT1 and KPTN), providing novel biological insight into the roles of these molecules in neuronal structure and brain function. Additionally, the role of mutations in SNIP1 as a cause of severe syndromic NDD were confirmed, contributing to the understanding of the clinical variability of this condition. Finally, improved characterisation of the genetic and epigenetic outcomes in DNMT3A-overgrowth syndrome and intellectual disability (OGID) were made possible through the study of a gonosomal mutation in a large Amish family with multiple affected individuals. The amalgamation of the work detailed in this thesis expands the scientific and medical understanding of the molecular aetiology of NDDs, and improves genetic testing and management strategies for Amish patients as well as families worldwide with these forms of NDDs.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.753988  DOI: Not available
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