Genetic landscape of early-onset dementia in Hungary.

Introduction: Early-onset dementias (EOD) are predominantly genetically determined, but the underlying disease-causing alterations are often unknown. The most frequent forms of EODs are early-onset Alzheimer's disease (EOAD) and frontotemporal dementia (FTD).

Patients: This study included 120 Hungarian patients with EOD (48 familial and 72 sporadic) which had a diagnosis of EOAD (n = 49), FTD (n = 49), or atypical dementia (n = 22).

The Role of the Rare Variants in the Genes Encoding the Alpha-Ketoglutarate Dehydrogenase in Alzheimer's Disease.

There is increasing evidence that several mitochondrial abnormalities are present in the brains of patients with Alzheimer's disease (AD). Decreased alpha-ketoglutarate dehydrogenase complex (αKGDHc) activity was identified in some patients with AD. The αKGDHc is a key enzyme in the Krebs cycle.

[Hereditary Parkinson’s disease as a new clinical manifestation of the damaged POLG gene].

The protein product of the nuclear-encoded POLG gene plays a key role in the maintenance of mitochondrial DNA replication, and its failure causes multi-system diseases with varying severity. The clinical spectrum is extremely wide, and the most common symptoms include ptosis, myoclonus, epilepsy, myopathy, sensory ataxia, parkinsonism, cognitive decline and infertility. Now, it is known that mitochondrial dysfunction in Parkinson's disease plays a key role in the loss of dopaminergic neurons in the substantia nigra.

Broadening the phenotype of the TWNK gene associated Perrault syndrome.

Background: Perrault syndrome is a genetically heterogenous, very rare disease, characterized clinically by sensorineural hearing loss, ovarian dysfunction and neurological symptoms. We present the case of a 33 years old female patient with TWNK-associated Perrault syndrome. The TWNK gene is coding the mitochondrial protein Twinkle and currently there are only two reports characterizing the phenotype of TWNK-associated Perrault syndrome.

Comprehensive Analysis of Rare Variants of 101 Autism-Linked Genes in a Hungarian Cohort of Autism Spectrum Disorder Patients.

Background: Autism spectrum disorder (ASD) is genetically and phenotypically heterogeneous. Former genetic studies suggested that both common and rare genetic variants play a role in the etiology. In this study, we aimed to analyze rare variants detected by next generation sequencing (NGS) in an autism cohort from Hungary.

Whole mitochondrial genome diversity in two Hungarian populations.

Complete mitochondrial genomics is an effective tool for studying the demographic history of human populations, but there is still a deficit of mitogenomic data in European populations. In this paper, we present results of study of variability of 80 complete mitochondrial genomes in two Hungarian populations from eastern part of Hungary (Szeged and Debrecen areas). The genetic diversity of Hungarian mitogenomes is remarkably high, reaching 99.

Mitochondrial dysfunction and autism: comprehensive genetic analyses of children with autism and mtDNA deletion.

Background: The etiology of autism spectrum disorders (ASD) is very heterogeneous. Mitochondrial dysfunction has been described in ASD; however, primary mitochondrial disease has been genetically proven in a small subset of patients. The main goal of the present study was to investigate correlations between mitochondrial DNA (mtDNA) changes and alterations of genes associated with mtDNA maintenance or ASD.

Targeted next generation sequencing of a panel of autism-related genes identifies an EHMT1 mutation in a Kleefstra syndrome patient with autism and normal intellectual performance.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with unknown genetic and environmental causation in most of the affected individuals. On the other hand, there are a growing number of ASD-associated syndromes, where the exact genetic origin can be revealed. Here we report a method, which included the targeted next generation sequencing (NGS) and filtering of 101 ASD associated genes, followed by database search.

Genetic background of the hereditary spastic paraplegia phenotypes in Hungary - An analysis of 58 probands.

Background: Hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative diseases with progressive lower limb spasticity and weakness. The aim of this study is to determine the frequency of different SPG mutations in Hungarian patients, and to provide further genotype-phenotype correlations for the known HSP causing genes.

Methods: We carried out genetic testing for 58 probands with clinical characteristics of HSP.

Asian-specific mitochondrial genome polymorphism (9-bp deletion) in Hungarian patients with mitochondrial disease.

A 9-bp deletion of the mtDNA is known as an anthropological marker of people with East-Asian origin. This 9-bp mtDNA deletion was analyzed in 1073 Hungarians with suspected mitochondrial disease and in 468 healthy control individuals. Fourteen cases with the 9-bp deletion were found in the cohort of mitochondrial patients, and one individual from 468 controls.

Retrospective assessment of the most common mitochondrial DNA mutations in a large Hungarian cohort of suspect mitochondrial cases.

Prevalence estimations for mitochondrial disorders still vary widely and only few epidemiologic studies have been carried out so far. With the present work we aim to give a comprehensive overview about frequencies of the most common mitochondrial mutations in Hungarian patients. A total of 1328 patients were tested between 1999 and 2012.

Coexisting huntingtin and SCA8 repeat expansion: case report of a severe complex neurodegenerative syndrome.

We report the case of a 29 year old woman with a complex movement disorder syndrome due to the combination of coexisting pathological triplet repeat expansions of huntingtin and ATXN8 genes. The disease course was characterized by mental disturbances including cognitive decline and changes in personality starting at the age of 12 years, followed by twisting motions, intentional tremor and gait ataxia. Later Parkinsonian symptoms of micrographia, bradykinesia, muscle rigidity and mental decline became dominant.

Novel heteroplasmic mutation in the anticodon stem of mitochondrial tRNA(Lys) associated with dystonia and stroke-like episodes.

Objectives: We report a novel heteroplasmic mitochondrial tRNA(Lys) mutation associated with dystonia, stroke-like episodes, sensorineural hearing loss and epilepsy in a Hungarian family.

Material And Methods: A 16-year-old boy, his brother and mother were investigated. Thorough clinical investigation as well as electrophysiological, neuroradiological and myopathological examinations were performed.

Bcl-2 or bcl-XL gene therapy increases neural plasticity proteins nestin and c-fos expression in PC12 cells.

The anti-apoptotic gene replacements could be an option in preventing hypoxia-induced neuronal loss. In this paper we tested the effect of anti-apoptosis (bcl-2 and bcl-XL) gene transfer on cell plasticity. Nestin, synapsin-1 and c-fos genes and proteins expression were measured in PC12 cells in normal condition, and after hypoxia/re-oxygenation.

[Maternally inherited diabetes mellitus, deafness, chronic progressive external ophthalmoplegia and myopathy as the result of A3243G mutation of mtDNA].

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome are caused mainly by the A3243G mutation of the mitochondrial genome. The A3243G substitution of mitochondrial DNA (mtDNA) is also responsible for various, other clinical phenotypes and syndromes. Here we report the case of a 33-year-old woman, with childhood onset ophthalmoplegia externa, progressive, generalised exercise intolerability, muscle weakness, hypacusis and diabetes mellitus as the symptoms of mitochondrial disease.