| Summary: | Abstract Ophthalmological manifestations are common in mitochondrial diseases. All parts of the eye can be affected, and symptoms can appear at any age making diagnostics challenging. The aims of this thesis were to study a prevalence of a genetically defined Leber hereditary optic neuropathy (LHON) in Northern Finland among adult and child populations and to identify novel genetic aetiologies and risk factors for ophthalmological manifestations of childhood-onset mitochondrial diseases. The study population comprised two retrospective patient cohorts: 42 adult patients with aetiologically undefined bilateral optic atrophy, and 355 children with at least one of five common mitochondrial ocular symptoms: optic neuropathy, retinal degeneration, nystagmus, ophthalmoplegia or ptosis. Only children without specific syndromes or genetically verified diseases were eligible (98 patients), and 38 participated in further studies on mitochondrial DNA and targeted nuclear genes. Furthermore, whole exome sequencing and studies on patient-derived tissue samples were performed to identify genetic aetiology of an infantile-onset, fatal multiorgan disease with optic neuropathy, pigmentary retinopathy, and nystagmus. The study revealed that LHON prevalence in Northern Finland is the same as in other western countries. In all, 73% of paediatric patients (n= 257 / 355) had defined diseases or syndromes related to chromosomal alterations or known pathogenic nDNA variants. In 38 patients, the association between retinal degeneration and MT-ATP6 variants was revealed. Nystagmus, optic neuropathy and retinal degeneration were found to be possible signs of mitochondrial diseases, especially when developmental problems or a positive family history were also present. Furthermore, genetic and functional data on an early-onset progressive encephalomyopathy with ocular defects suggested a phenotype associated with DHX16 variant. This thesis highlights the increasing role of genetic analyses and multidisciplinary academic collaboration in ...
|
|---|