Altered mitochondrial DNA (mtDNA) methylation has been detected in several human pathologies, although little attention has been given to neurodegenerative diseases. Recently, altered methylation levels of the mitochondrial displacement loop (D-loop) region, which regulates mtDNA replication, were observed in peripheral blood cells of Alzheimer’s disease and amyotrophic lateral sclerosis patients. However, nothing is yet known about D-loop region methylation levels in peripheral blood of Parkinson’s disease (PD) patients. In the current study, we investigated D-loop methylation levels and mtDNA copy number in peripheral blood of 30 PD patients and 30 age- and sex-matched control subjects. DNA methylation analyses have been performed by means of methylation-sensitive high-resolution melting (MS-HRM) and pyrosequencing techniques, while mtDNA copy number was analyzed by quantitative PCR. MS-HRM and pyrosequencing analyses provided very similar D-loop methylation levels in PD patients and control subjects, and no differences between the two groups have been observed. Treatment with L-dopa and duration of the disease had no effect on D-loop methylation levels in PD patients. Additionally, mtDNA copy number did not differ between PD patients and control subjects. Current results suggest that D-loop methylation levels are not altered in peripheral blood of PD patients nor influenced by dopaminergic treatment.

Background: Familial adult myoclonus epilepsy (FAME) is a rare autosomal dominant disorder caused by the same intronic TTTTA/TTTCA repeat expansion in seven distinct genes. TTTTA‐only expansions are benign, whereas those containing TTTCA insertions are pathogenic.Objective: We investigated the genetic basis of dominant cortical myoclonus without seizures in two unrelated families.Methods: Repeat‐primed polymerase chain reaction (PCR), long‐range PCR, and nanopore sequencing were used to detect and characterize expansions at known FAME loci.Results: We identified a novel repeat expansion in MARCHF6, comprising 388 to 454 elongated TTTTA repeats and 5 to 11 TTTCA repeats at the 3′‐terminus, segregating with cortical myoclonus in 8 affected individuals. This configuration shows meiotic stability but low‐level somatic variability in blood. We observed an inverse correlation between the number of TTTCA repeats and the age at myoclonus onset.Conclusions: These findings indicate that as little as five TTTCA repeats combined with expanded TTTTA repeats can cause cortical myoclonus without epilepsy, highlighting the potential mechanisms underlying FAME pathophysiology. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: The diagnosis of genetic hyperkinetic movement disorders has become increasingly more complex as new genes are discovered and technologies offer new diagnostic possibilities. As a result, the choice of appropriate gene testing and the interpretation of the results can become difficult to navigate for movement disorder experts and clinicians. In parallel, research is becoming crucial to pair with clinical assessments in order to explore advanced sequencing technologies and allow new genes discovery. Methods: Systematic review of genetic forms of hyperkinetic movement disorders and of the most relevant genetic terminology was performed. Results: Comprehensive descriptions of genetic lexicon, testing selection, and complex genetic findings related to hyperkinetic movement disorders are reported. Discussion: Here we discuss the terminology of genetic diagnosis that is now part of the clinical practice, the difficulties related to the interpretation of complex genetic results, and provide guidance and tips for gene testing selection in order not to miss important diagnosis of genetic hyperkinetic movement disorders. Highlights To review the most relevant lexicon related to genetic diagnosis, approach to gene testing, testing selection, and complex genetic findings in genetic hyperkinetic movement disorders.