Genetic eye diseases, focus on ophthalmological manifestations of mitochondrial diseases

Thesis event information

Date and time of the thesis defence

Place of the thesis defence

Faculty of Medicine, Leena Palotie -hall, Aapistie 5A

Topic of the dissertation

Genetic eye diseases, focus on ophthalmological manifestations of mitochondrial diseases

Doctoral candidate

Licentiate in Medicine Paula Widgren

Faculty and unit

University of Oulu Graduate School, Faculty of Medicine, Research Unit of Clinical Medicine

Subject of study



docent Joni A Turunen, Helsinki University Hospital


professor Johanna Uusimaa, Oulu University Hospital

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Genetic eye diseases, focus on ophthalmological manifestations of mitochondrial diseases

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. 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. Furthermore, the younger the child is, the more difficult the examination is.
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, 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, being one of the most common mitochondrial disease. In paediatric 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 disease diagnostics.
Last updated: 23.1.2024