Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
Results
Showing 1 to 18 of 18 for “"Pathogenic variant"”.
-
Assessing Genetic Counselors' Clinical Approach and Practices Regarding Pathogenic/Likely Pathogenic Variant Downgrades
<p>Although rare, variant downgrades from a pathogenic/likely pathogenic (P/LP) variant to a variant of uncertain significance can have a significant impact on patients and their families in the clinical cancer setting. However, there is a lack of literature about how to approach these potentially …
-
Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease
<p>Heterozygous pathogenic variants in <em>ACTA2</em>, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. <em>De novo</em> missense variants disrupting <em>ACTA2 </em>arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction …
-
Second primary cancers following breast cancer in the general population and in BRCA1 and BRCA2 pathogenic variant carriers
… cancer (BC) survivors carrying BRCA1 or BRCA2 pathogenic variants (PVs) are uncertain. There is also little evidence for how SPC risks following BC vary by sociodemographic factors, treatments, or the pathology of the first BC. My objectives were to estimate combined and site-specific SPC risks …
-
The characterization of Lowe Syndrome in a South African cohort
… all affected boys will be hemizygous for a pathogenic variant in the OCRL (NM_000276.4 c.2615delC) gene. We present a clinical and molecular characterization of an extended multiplex family of three affected boys with Lowe Syndrome and describe a novel variant, predicted to be pathogenic, in …
-
Effects of the MYH7 R369Q Dilated Cardiomyopathy-causing Mutation on Myosin Crossbridge Kinetics and Cardiomyocyte Contractility
The R369Q mutation in the MYH7 gene is a likely pathogenic variant of familial dilated cardiomyopathy (DCM). This mutation is located in loop 4 of β-myosin heavy chain actin-binding surface and may alter actin-myosin interaction that facilitates cardiomyocyte contraction. There are limited insights …
-
Investigation of the genetic basis of multiple primary renal tumours
… in 534 individuals. The presence/absence of variants in cancer susceptibility genes (CSGs) from exome/genome sequencing was then correlated with data on age, sex, tumour types and RCC histopathology in 93 participants with MPRT and 441 with MPT:RCC+X. 7.5% of participants with MPRT and 6.1% …
-
Building capacity for diagnosis of Primary Ciliary Dyskinesia in South Africa: a descriptive study
… black Africans were homozygous for the same pathogenic variant in DNAAF3. Conclusion: Using a range of diagnostic modalities, the study has identified PCD cases who would have otherwise been missed or incorrectly diagnosed
-
Consequences of Pathogenic Mitochondrial DNA Mutations in Cancer Progression
… cancer cell lines with defined pathogenic mutations, and secondly, by the establishment of a collection of patient tumor xenograft models with varied mtDNA status. Chapter two details the development of a new cytoplasmic hybrid (cybrid) generation method that simplifies the …
-
Genetic Counselors' Approaches to Direct-To-Consumer Genetic Testing For Hereditary Breast Cancer
… or TPI data that reported a <em>BRCA1/2 </em>pathogenic variant. We recruited 80 GCs specializing in hereditary cancer and administered a survey that assessed their testing strategy for probands from three hypothetical case scenarios with variable personal and family histories of cancer. The …
-
Parallels and Divergences in Multisystem Proteinopathy Genes: Stress Granules, Autophagy, and Myogenic Deficits
… involvement, we asked; what are the unifying pathogenic features of MSP? To address this, we examined three areas of interest: stress granules, autophagy, and myogenesis. The currently identified roster of MSP genes have several structural and functional commonalities which fall into two …
-
"Interrogating the genomic and metabolomic landscape of pseudohypoxic phaeochromocytoma and paraganglioma syndromes"
… genes. Identifying individuals carrying a pathogenic variant in one of these genes leads to lifelong surveillance. Despite the low tumour penetrance, SDHx deficient PPGLs are associated with an aggressive disease course, with a 5-year overall survival of 50% in individuals with metastatic …
-
Why do allelic variants of the mitochondrial chaperone SCO1 cause clinically heterogeneous forms of disease? A mouse model and proximity ligation study
… outcomes, it remains unclear why allelic variants unique to each SCO1 pedigree primarily affect heart, liver or brain function. I therefore created and phenotyped three whole body Sco1 knockin mouse models harbouring one or two alleles of the murine equivalent of the pathogenic SCO1 P174L, …
-
DISSECTING THE POLYGENIC LANDSCAPE OF HUMAN COMPLEX TRAITS AND DISEASES IN A SOUTHERN ITALIAN COHORT
… the combined effects of common and rare genetic variants, yet their contribution to risk is still poorly characterised in Southern European populations. This thesis addresses this gap by analysing the genetic architecture of traits and diseases in Italy, leveraging the Moli-sani cohort, a large …
-
Common genetic variation and spliceosome variants in rare developmental disorders
… caused by single, deleterious, protein- coding variants, evidence suggests that common variants also contribute to risk for rare, neurodevelopmental disorders (NDDs). These are likely affecting the penetrance of protein-coding variants as well as expressivity, posing a major challenge in the …
-
Pathogenicity assessment of genetic variants in von Willebrand disease using quantitative, qualitative, and functional approaches
… cells (ECs). VWD is caused by rare DNA sequence variants in the VWF gene. However, coupling genotype with phenotype is complicated by factors including incomplete penetrance and the trans-acting effect of the ABO histo-group. High throughput sequencing (HTS) is becoming the standard of care for …
-
Genetic basis of inherited kidney and related tumours
… for the molecular investigation, germline variant interpretation and clinical management of patients with syndromic and non-syndromic inherited RCC are suggested. A variety of investigative approaches were utilised for this thesis. Firstly, a service evaluation was undertaken which showed a …
-
Genetic and functional studies in inherited platelet disorders
… loci associated with platelet traits. Common variants, with a minor allele frequency (MAF) ≥1% are associated with mild variation in platelet parameters, whereas rare variants (MAF <1%) are associated with extreme phenotypes and inherited platelet disorders (IPDs). The polygenic score (PGS) …
-
Identifying Genes and Novel Variants Involved in Nonsyndromic Hearing Impairment, and Assessment of the Psychosocial Burden of Hearing Impairment in Cameroon
… European and Asian populations have identified pathogenic variants in GJB2 (MIM: 121011), and GJB6 (MIM: 604418) genes as the major contributors to autosomal recessive NSHI (ARNSHI). The genetic aetiology of HI in Cameroon is unclear, as previous studies have found no contribution of GJB2 and …