Gene Variants Are a Frequent Cause of a Rare Disease: Leber Hereditary Optic Neuropathy in Polish Patients.

Leber hereditary optic neuropathy (LHON) is a rare disorder causing a sudden painless loss of visual acuity in one or both eyes, affecting young males in their second to third decade of life. The molecular background of the LHON is up to 90%, genetically defined by a point mutation in mitochondrial DNA. Recently, an autosomal recessive form of LHON (LHONAR1, arLHON) has been discovered, caused by biallelic variants in the gene.

Mitochondrial Genome Variation in Polish Elite Athletes.

Energy efficiency is one of the fundamental athletic performance-affecting features of the cell and the organism as a whole. Mitochondrial DNA (mtDNA) variants and haplogroups have been linked to the successful practice of various sports, but despite numerous studies, understanding of the correlation is far from being comprehensive. In this study, the mtDNA sequence and copy number were determined for 99 outstanding Polish male athletes performing in power (n = 52) or endurance sports (n = 47) and 100 controls.

Vascular Changes in the Macula of Patients after Previous Episodes of Vision Loss Due to Leber Hereditary Optic Neuropathy and Non-Arteritic Ischemic Optic Neuropathy.

Purpose: to assess the vasculature and thickness of the macula using OCT-A in patients who had experienced a previous episode of Leber hereditary optic neuropathy (LHON) or non-arteritic anterior ischemic optic neuropathy (NA-AION).

Methods: twelve eyes with chronic LHON and ten eyes with chronic NA-AION and eight NA-AION fellow eyes were examined using OCT-A. The vessel density was measured in the superficial and deep plexus of the retina.

To Be a Champion of the 24-h Ultramarathon Race. If Not the Heart ... Mosaic Theory?

This comprehensive case analysis aimed to identify the features enabling a runner to achieve championship in 24-h ultramarathon (UM) races. A 36-year-old, multiple medalist of the World Championships in 24-h running, was assessed before, one and 10 days after a 24-h run. Results of his extensive laboratory and cardiological diagnostics with transthoracic echocardiography (TTE) and a one-time cardiopulmonary exercise test (CPET) were analyzed.

Progressive External Ophthalmoplegia in Polish Patients-From Clinical Evaluation to Genetic Confirmation.

Mitochondrial encephalomyopathies comprise a group of heterogeneous disorders resulting from impaired oxidative phosphorylation (OxPhos). Among a variety of symptoms progressive external ophthalmoplegia (PEO) seems to be the most common. The aim of this study is to present clinical and genetic characteristics of Polish patients with PEO.

Mitochondrial genome variation in male LHON patients with the m.11778G > A mutation.

Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder with symptoms limited to a single tissue, optic nerve, resulting in vision loss. In the majority of cases it is caused by one of three point mutations in mitochondrial DNA (mtDNA) but their presence is not sufficient for disease development, since ~50% of men and ~10% women who carry them are affected. Thus additional modifying factors must exist.

Testosterone increases apoptotic cell death and decreases mitophagy in Leber's hereditary optic neuropathy cells.

Leber's hereditary optic neuropathy (LHON) is one of the most common mitochondrial diseases caused by point mutations in mitochondrial DNA (mtDNA). The majority of diagnosed LHON cases are caused by a point mutation at position 11,778 in the mitochondrial genome. LHON mainly affects young men in their 20s and 30s with usually poor visual prognosis.

RNase H1 Regulates Mitochondrial Transcription and Translation the Degradation of 7S RNA.

RNase H1 is able to recognize DNA/RNA heteroduplexes and to degrade their RNA component. As a consequence, it has been implicated in different aspects of mtDNA replication such as primer formation, primer removal, and replication termination, and significant differences have been reported between control and mutant skin fibroblasts from patients. However, neither mtDNA depletion nor the presence of deletions have been described in skin fibroblasts while still presenting signs of mitochondrial dysfunction (lower mitochondrial membrane potential, reduced oxygen consumption, slow growth in galactose).

Whole exome sequencing identifies a homozygous POLG2 missense variant in an adult patient presenting with optic atrophy, movement disorders, premature ovarian failure and mitochondrial DNA depletion.

POLG2 associated disorders belong to the group of mitochondrial DNA (mtDNA) diseases and present with a heterogeneous clinical spectrum, various age of onset, and disease severity. We report a 39-year old female presenting with childhood-onset and progressive neuroophthalmic manifestation with optic atrophy, mixed polyneuropathy, spinal and cerebellar ataxia and generalized chorea associated with mtDNA depletion. Whole-exome sequencing identified an ultra-rare homozygous missense mutation located at Chr17: 062474101-C > A (p.

New mtDNA Association Model, MutPred Variant Load, Suggests Individuals With Multiple Mildly Deleterious mtDNA Variants Are More Likely to Suffer From Atherosclerosis.

The etiology of common complex diseases is multifactorial, involving both genetic, and environmental factors. A role for mitochondrial dysfunction and mitochondrial DNA (mtDNA) variation has been suggested in the pathogenesis of common complex traits. The aim of this study was to investigate a potential role of mtDNA variants in the development of obesity, diabetes, and atherosclerosis in the Polish population.

[Mitochondrial diseases 2018].

Mitochondrial diseases are caused by dysfunction of the mitochondrial oxidative phosphorylation system and can be the result of mutations both in mitochondrial DNA and in nuclear DNA. Mitochondrial diseases collectively describe a diverse group of heritable disorders, which may present at any age and have a wide spectrum of clinical manifestations. This leads to highly variable presentations, making the diagnosis of mitochondrial diseases challenging.

The frequency of mitochondrial polymerase gamma related disorders in a large Polish population cohort.

Diseases related to DNA polymerase gamma dysfunction comprise of heterogeneous clinical presentations with variable severity and age of onset. Molecular screening for the common POLG variants: p.Ala467Thr, p.

Investigation of whole mitochondrial genome variation in normal tension glaucoma.

Glaucoma is one of the leading causes of visual impairment and blindness worldwide. However, the cause of retinal ganglion cell loss and damage of the optic nerve in its pathogenesis is largely unknown. The high energy demands of these cells may reflect their strong dependence on mitochondrial function and thus sensitivity to mitochondrial defects.

Analysis of Visual Field Defects Obtained with Semiautomated Kinetic Perimetry in Patients with Leber Hereditary Optic Neuropathy.

Purpose: To analyse visual field (VF) defects obtained using semiautomated kinetic perimetry (SKP) in patients suffering from Leber hereditary optic neuropathy (LHON).

Methods: Twenty-two eyes of eleven consecutive LHON male patients with confirmed mitochondrial 11778G>A DNA mutation were prospectively examined with the V4e stimulus of SKP in both eyes. The mean time after the onset of LHON was one year.

Nuclear genes involved in mitochondrial diseases caused by instability of mitochondrial DNA.

Mitochondrial diseases are defined by a respiratory chain dysfunction and in most of the cases manifest as multisystem disorders with predominant expression in muscles and nerves and may be caused by mutations in mitochondrial (mtDNA) or nuclear (nDNA) genomes. Most of the proteins involved in respiratory chain function are nuclear encoded, although 13 subunits of respiratory chain complexes (together with 2 rRNAs and 22 tRNAs necessary for their translation) encoded by mtDNA are essential for cell function. nDNA encodes not only respiratory chain subunits but also all the proteins responsible for mtDNA maintenance, especially those involved in replication, as well as other proteins necessary for the transcription and copy number control of this multicopy genome.

Mitochondrial DNA levels in Huntington disease leukocytes and dermal fibroblasts.

Huntington disease (HD) is an inherited neurodegenerative disorder caused by mutations in the huntingtin gene. Involvement of mitochondrial dysfunctions in, and especially influence of the level of mitochondrial DNA (mtDNA) on, development of this disease is unclear. Here, samples of blood from 84 HD patients and 79 controls, and dermal fibroblasts from 10 HD patients and 9 controls were analysed for mtDNA levels.

Mitochondrial DNA in pediatric leukemia patients.

Numerous studies of mitochondrial DNA (mtDNA) in cancer have shown differences between mtDNA sequences in tumor and normal tissue and at various stages of cancer treatment in the same patient. However, there is little data on acute lymphoblastic leukemia (ALL), the most common type of leukemia in children. In this study we compared mitochondrial sequence variation in the D-loop region and in 5 genes of mtDNA in bone marrow samples of 6 pediatric patients with ALL at various stages of therapy.

Identification of the first in Poland CACNA1A gene mutation in familial hemiplegic migraine. Case report.

Introduction: Migraine is a common neurological disorder characterized by a particular phenotype, complex pathophysiology and a heterogeneous genetic background. Among several heritable forms, familial hemiplegic migraine is the best described one. In the majority of cases it is caused by mutations in one of three different genes.

Yeast model analysis of novel polymerase gamma variants found in patients with autosomal recessive mitochondrial disease.

Replication of the mitochondrial genome depends on the single DNA polymerase (pol gamma). Mutations in the POLG gene, encoding the catalytic subunit of the human polymerase gamma, have been linked to a wide variety of mitochondrial disorders that show remarkable heterogeneity, with more than 200 sequence variants, often very rare, found in patients. The pathogenicity and dominance status of many such mutations remain, however, unclear.

Mitochondrial DNA Polymerase γ Mutations and Their Implications in mtDNA Alterations in Colorectal Cancer.

Mitochondrial DNA was found to be highly mutated in colorectal cancer cells. One of the key molecules involved in the maintenance of the mitochondrial genome is the nuclear-encoded polymerase gamma. The aim of our study was to determine if there is a link between polymorphisms within the polymerase gamma gene (POLG) and somatic mutations within the mitochondrial genome in cancer cells.

Changing phenotypic expression in a patient with a mitochondrial encephalopathy due to 13042G>A de novo mutation--a 5 year follow up.

Mutations in NADH dehydrogenase (ND) subunits of complex I lead to mitochondrial encephalomyopathies associated with various phenotypes. This report aims to present the patient's clinical symptomatology in the context of a very rare 13042G>A de novo mutation and with an emphasis on changing phenotypic expression and pronounced, long-standing response to levetiracetam.

Leber hereditary optic neuropathy - historical report in comparison with the current knowledge.

Leber hereditary optic neuropathy (LHON) is a genetic, maternally inherited disease caused by point mutations in the mitochondrial genome. LHON patients present with sudden, painless and usually bilateral loss of vision caused by optic nerve atrophy. The first clinical description of the disease was made by Theodor Leber, a German ophthalmologist, in 1871.

m.3635G>A mutation as a cause of Leber hereditary optic neuropathy.

Over 90% of Leber's hereditary optic neuropathy (LHON) is caused by one of three mtDNA mutations (m.11778A>G, m.3460G>A, m.

Mitochondrial encephalomyopathy: towards diagnosis. A case report.

Mitochondrial diseases may cause a wide range of central and peripheral nervous system disorders, as well as muscle disorders. The diagnostic workup routinely includes electrophysiological, morphological, neuroimaging and genetic studies. In some cases, the diagnosis may be ascertained only when mitochondrial DNA (mtDNA) examination in the muscle is performed.