A5055881297- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Metabolism and Genetic Disorders
- Congenital Heart Disease Studies
- Neonatal and fetal brain pathology
- Lysosomal Storage Disorders Research
- Glioma Diagnosis and Treatment
- ATP Synthase and ATPases Research
- Hereditary Neurological Disorders
- Childhood Cancer Survivors' Quality of Life
- RNA regulation and disease
- Herpesvirus Infections and Treatments
- DNA Repair Mechanisms
- Advanced Neuroimaging Techniques and Applications
- Meningioma and schwannoma management
- Congenital heart defects research
- Fetal and Pediatric Neurological Disorders
- Genomics and Rare Diseases
- Acute Lymphoblastic Leukemia research
- Viral Infections and Immunology Research
- Neuroblastoma Research and Treatments
- Cytomegalovirus and herpesvirus research
- Research in Social Sciences
- Infant Development and Preterm Care
- Neurological Complications and Syndromes
Helsinki University Hospital
2015-2024
University of Helsinki
2015-2024
Institute for Molecular Medicine Finland
1996-2020
St George's, University of London
2020
Helsinki Children's Hospital
2003-2018
Children's Hospital
2008-2018
Helsinki Art Museum
2018
Hospital District of Helsinki and Uusimaa
2001-2017
National Institutes of Natural Sciences
2016
National Institute for Physiological Sciences
2016
Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite fact that most common phenotype disorders in children, longitudinal natural history data missing. This study was undertaken to assess phenotypic and genotypic spectrum patients syndrome, characterise clinical course identify predictors survival large cohort patients.This retrospective have been followed at eight centers...
Background: Epidemiologic studies of the families patients with ataxia-telangiectasia (A-T), a recessive genetic neurologic disorder caused by mutation ATM gene, suggest that heterozygous carriers an are at increased risk cancer. A population-based study cancer incidence in A-T unbiased selection and tracing relatives would confirm this hypothesis. Methods: We conducted Nordic countries 1218 blood 56 from 50 families. The were identified population registries, occurrence was determined...
Infantile onset spinocerebellar ataxia (IOSCA) (MIM 271245) is a severe autosomal recessively inherited neurodegenerative disorder characterized by progressive atrophy of the cerebellum, brain stem and spinal cord sensory axonal neuropathy. We report here molecular background this disease based on positional cloning/candidate approach defective gene. Having established linkage to chromosome 10q24, we restricted critical DNA region using single nucleotide polymorphism-based haplotypes. After...
Twinkle is a mitochondrial replicative helicase, the mutations of which have been associated with autosomal dominant progressive external ophthalmoplegia (adPEO), and recessively inherited infantile onset spinocerebellar ataxia (IOSCA). We report here new phenotype in two siblings compound heterozygous (A318T Y508C), characterized by severe early encephalopathy signs liver involvement. The clinical manifestations included hypotonia, athetosis, sensory neuropathy, ataxia, hearing deficit,...
Infantile-onset spinocerebellar ataxia (IOSCA) is a severe neurodegenerative disorder caused by the recessive mutation in PEO1, leading to an Y508C change mitochondrial helicase Twinkle, its domain. However, no dysfunction has been found this disease. We studied here consequences of IOSCA for central nervous system, as well vitro performance mutant protein. The results mtDNA analyses were compared findings similar juvenile or adult-onset syndrome, syndrome (MIRAS), W748S DNA polymerase...
The C10orf2 gene encodes the mitochondrial DNA helicase Twinkle, which is one of proteins important for maintenance. Dominant mutations cause multiple deletions and progressive external ophthalmoplegia, but recent findings associate recessive with depletion encephalopathy or hepatoencephalopathy. latter clinical phenotypes resemble those associated POLG1 mutations. We have previously described patients infantile onset spinocerebellar ataxia (MIM271245) caused either by homozygous (Y508C)...
De novo mutations in ATAD3A (ATPase family AAA-domain containing protein 3A) were recently found to cause a neurological syndrome with developmental delay, hypotonia, spasticity, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy. Using whole-exome sequencing, we identified dominantly inherited heterozygous variant c.1064G > A (p.G355D) mother presenting hereditary spastic paraplegia (HSP) neuropathy her son dyskinetic cerebral palsy, both disease onset childhood. HSP is...
Inherited peripheral neuropathies are a heterogeneous group of disorders that can affect patients all ages. Children with inherited neuropathy often develop severe disability, but the genetic causes recessive early-onset axonal not fully known. We have taken whole-exome sequencing approach to identify causative disease mutations in single neuropathy. Here, we report compound heterozygous tripartite motif containing 2 (TRIM2) gene patient childhood-onset neuropathy, low weight and small...
Background Leigh syndrome is a phenotypically and genetically heterogeneous mitochondrial disorder. While some genetic defects are associated with well-described phenotypes, phenotype-genotype correlations in not fully explored. Objective We aimed to identify large cohort of systematically evaluated patients. Methods studied 96 patients confirmed diagnosed followed eight European centres specialising diseases. Results found that ataxia, ophthalmoplegia cardiomyopathy were more prevalent...
Research Article29 October 2018Open Access Transparent process Metabolomes of mitochondrial diseases and inclusion body myositis patients: treatment targets biomarkers Jana Buzkova Programs Unit, Molecular Neurology, Biomedicum-Helsinki, University Helsinki, Finland Search for more papers by this author Joni Nikkanen orcid.org/0000-0001-7099-4061 Sofia Ahola Anna H Hakonen Ksenia Sevastianova Department Medicine, Helsinki Hospital, Minerva Foundation Institute Medical Research, Topi Hovinen...
Congenital cytomegalovirus (cCMV) infection is the most common congenital and causes significant morbidity. This study was undertaken to evaluate benefits of screening newborns for cCMV understand disease burden in Finland.Infants born Helsinki area hospitals were screened CMV by testing their saliva with a real-time polymerase chain reaction assay. The CMV-positive infants matched controls monitored determine neurodevelopmental, audiological, ophthalmological outcomes at 18 months age....
We aimed to decipher the molecular genetic basis of disease in a cohort children with uniform clinical presentation neonatal irritability, spastic or dystonic quadriplegia, virtually absent psychomotor development, axonal neuropathy, and elevated blood/CSF lactate.We performed whole-exome sequencing blood DNA from index patients. Detected compound heterozygous mutations were confirmed by Sanger sequencing. Structural predictions bacterial activity assay evaluate functional consequences...
Abstract We studied 14 individuals with partial deletions of the long arm chromosome 18, including terminal and interstitial de novo inherited deletions. Study participants were examined clinically by brain MRI. The size deletion was determined segregation analysis using microsatellite markers. observed that phenotype highly variable, even in two families three 1st degree relatives. Among individuals, general intelligence varied from normal to severe mental retardation. more common features...
<b>Background: </b> Extensive cerebral calcifications and leukoencephalopathy have been reported in two rare disorders Coats plus with cysts. In the latter, a progressive formation of parenchymal brain cysts is special feature, whereas characterized by intrauterine growth retardation, bilateral retinal telangiectasias exudations (Coats disease), sparse hair, dysplastic nails without cyst formation. <b>Methods: We identified 13 patients, including pairs siblings, extensive...
<h3>Background</h3> Leucoencephalopathy with brain stem and spinal cord involvement high lactate (LBSL) was first defined by characteristic magnetic resonance imaging spectroscopic findings. The clinical features include childhood or juvenile onset slowly progressive ataxia, spasticity, dorsal column dysfunction, occasionally accompanied learning difficulties. Mutations in <i>DARS2</i>, encoding mitochondrial aspartyl-tRNA synthetase, were recently shown to cause LBSL. signs symptoms show...
Objective: Mitochondrial DNA polymerase γ ( POLG1 ) mutations in children often manifest as Alpers syndrome, whereas adults, a common manifestation is mitochondrial recessive ataxia syndrome (MIRAS) with severe epilepsy. Because some patients MIRAS have presented or epilepsy already childhood, we searched for neurologic manifestations childhood. Methods: We investigated 136 children, all clinically suspected to disease, one more of the following: ataxia, axonal neuropathy, without known...
Background: Both primary and non-primary maternal cytomegalovirus (CMV) infection during pregnancy can lead to vertical transmission. We evaluated the proportion of primary/non-primary infections among 26 babies with symptomatic congenital CMV born in Finland from 2000 2012.Methods: executed a database search on hospital records all five university hospitals identify infants infection. The preserved serum samples drawn at end first trimester were analysed for antibodies. Maternal was...
Central nervous system tumours constitute 25% of all childhood cancers; more than half are located in the posterior fossa and surgery is usually part therapy. One most disabling late effects tumour cerebellar mutism syndrome (CMS) which has been reported up to 39% patients but exact incidence uncertain since milder cases may be unrecognized. Recovery incomplete. Reported risk factors type, midline location brainstem involvement, aetiology, surgical other factors, clinical course strategies...