BACKGROUND AND PURPOSE Progressive external ophthalmoplegia (PEO) with Mendelian inheritance is a heterogeneous group of diseases associated with multiple deletions of mitochondrial DNA (mtDNA), which results from the disturbed replication and maintenance of mtDNA secondary to the mutations of nuclear genes including POLG, SLC25A4, C10ORF2, POLG2, OPA1, and RRM2B. The aim of this study was to i...

BACKGROUND & AIMS The etiology of acute liver failure (ALF) remains elusive in almost half of affected children. We hypothesized that inherited mitochondrial and fatty acid oxidation disorders were occult etiological factors in patients with idiopathic ALF and impaired energy metabolism. METHODS Twelve patients with elevated blood molar lactate/pyruvate ratio and indeterminate etiology were s...

Single-cell electrophoresis (comet assay) can be used to study DNA damage and repair mechanisms by measuring the frequency of strand breaks for individual cells in samples collected before and after exposure to a genotoxic agent. Because the distributions of the surrogates of DNA damage across cells in a sample vary in shape for different cell lines and followup times, standard hierarchical mod...

To highlight differences between early-onset and adult mitochondrial depletion syndromes (MDS) concerning etiology and genetic background, pathogenesis, phenotype, clinical presentation and their outcome. MDSs most frequently occur in neonates, infants, or juveniles and more rarely in adolescents or adults. Mutated genes phenotypically presenting with adult-onset MDS include POLG1, TK2, TyMP, R...

Genetic lesions causing human male infertility are manifold. Besides gross chromosomal aneuploidies and rearrangements, microdeletions and single gene defects can interfere with male fertility. Male fertility is not only dependent on genes controlling the male germ line but also on genes of the networks functional for male gonad development and male somatic development, respectively. It is popu...

Abstract Study question Is Next Generation Sequencing (NGS) an effective diagnostic tool for sperm abnormalities? Summary answer NGS male factor gene panel can be a potent discovering pathogenic variants linked to abnormalities. What is known already Male infertility, responsible half of infertility cases, often shows as absence or decreased count (azoospermia, criptozoospermia oligozoospermia)...

Nucleoside reverse transcriptase inhibitors (NRTIs) were the first drugs used to treat human immunodeficiency virus (HIV) the cause of acquired immunodeficiency syndrome. Development of severe mitochondrial toxicity has been well documented in patients infected with HIV and administered NRTIs. In vitro biochemical experiments have demonstrated that the replicative mitochondrial DNA (mtDNA) poly...

Aging is associated with conduit artery stiffening that is a risk factor for and can precede hypertension and ventricular dysfunction. Increases in mitochondria DNA (mtDNA) frequency have been correlated with aging. Mice with a mutation in the encoding domain (D257A) of a proof-reading deficient version of mtDNA polymerase-γ (POLG) have musculoskeletal features of premature aging and a shortene...

Charcot-Marie-Tooth (CMT) disease is the most prevalent inherited neuropathy. Today more than 40 CMT genes have been identified. Diagnosing heterogeneous diseases by conventional Sanger sequencing is time consuming and expensive. Thus, more efficient and less costly methods are needed in clinical diagnostics. We included a population based sample of 81 CMT families. Gene mutations had previousl...

BACKGROUND Age at natural menopause (ANM) is a complex trait with high heritability and is associated with several major hormonal-related diseases. Recently, several genome-wide association studies (GWAS), conducted exclusively among women of European ancestry, have discovered dozens of genetic loci influencing ANM. No study has been conducted to evaluate whether these findings can be generaliz...