A5058623427- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Genomics and Rare Diseases
- ATP Synthase and ATPases Research
- Genomic variations and chromosomal abnormalities
- Metabolomics and Mass Spectrometry Studies
- Hereditary Neurological Disorders
- Glycogen Storage Diseases and Myoclonus
- Genetic factors in colorectal cancer
- Neurological diseases and metabolism
- Cell death mechanisms and regulation
- RNA modifications and cancer
University of Cambridge
2023-2025
Cambridge University Hospitals NHS Foundation Trust
2021-2024
Addenbrooke's Hospital
2023
Genetic diagnosis of rare diseases requires accurate identification and interpretation genomic variants. Clinical molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree rare-disease data (94.5% exomes, 5.5% genomes), performed systematic reanalysis for 6,447 individuals (3,592 male, 2,855 female) with previously undiagnosed 6,004 families. We established a collaborative, two-level review...
Abstract Mutations in the mitochondrial or nuclear genomes are associated with a diverse group of human disorders characterized by impaired respiration. Within this group, an increasing number mutations have been identified genes involved RNA biology. The TEFM gene encodes transcription elongation factor responsible for enhancing processivity polymerase, POLRMT. We report first time that variants respiratory chain deficiency and wide range clinical presentations including myopathy treatable...
The diagnosis of mitochondrial DNA (mtDNA) diseases remains challenging with next-generation sequencing, where bioinformatic analysis is usually more focused on the nuclear genome. We developed a workflow for evaluation mtDNA and applied it in large European rare disease cohort (Solve-RD). A semi-automated pipeline MToolBox was used to filter unsolved Solve-RD variants after validating this exome datasets 42 individuals previously diagnosed variants. Variants were filtered based blood...
Abstract Background Peripheral neuropathies in mitochondrial disease are caused by mutations nuclear genes encoding proteins, or the genome. Whole exome genome sequencing enable parallel testing of and mtDNA genes, it has significantly advanced genetic diagnosis inherited diseases. Despite this, approximately 40% all Charcot-Marie-Tooth (CMT) cases remain undiagnosed. Methods The genome-phenome analysis platform (GPAP) RD-Connect was utilised to create a cohort 2087 patients with at least...
The genetic diagnosis of mitochondrial disorders is complicated by its and phenotypic complexity. Next generation sequencing techniques have much improved the diagnostic yield for these conditions. A cohort individuals with multiple respiratory chain deficiencies, reported in literature 10 years ago, had a rate 60% whole exome (WES) but 40% remained undiagnosed.
Background Leber Hereditary Optic Neuropathy (LHON) is the most common inherited mitochondrial disease characterized by bilateral, painless, subacute visual loss with a peak age of onset in second to third decade. Historically, LHON was thought be exclusively maternally due mutations DNA (mtDNA); however, recent studies have identified an autosomal recessive form (arLHON) caused point nuclear gene, DNAJC30 . Case Presentations In this study, we report cases three Eastern European individuals...