Teodora Barbarii

Background: Molecular testing for genetic movement disorders (MDs) increasingly relies on exome‐ or genome‐based virtual gene panels. In the absence of consensus guidelines, MD panel design remains heterogeneous across laboratories, with international variation in panel configuration and gene content. Objective: The aim of this work was to develop a reproducible framework for a unified MD panel design, generate a comprehensive, curated gene‐phenotype dataset, and evaluate clinical utility via targeted exome reanalysis. Methods: Candidate genes were extracted from multiple resources and assessed using predefined criteria for panel inclusion and gene‐disease validity. Genes were tiered as Green, Amber, or Red based on evidence strength. Phenotypic spectrum and age at onset were assessed for Green genes based on published literature. Newly added Green and Amber genes were investigated in 4,046 exomes from previously undiagnosed MD cases. Results: Among 2,090 extracted genes, 640 were selected. The final panel included 537 Green, 36 Amber, and 67 Red genes, expanding the prior panel by 283 genes and removing 42. Across Green genes, only 17% were linked to a single MD feature, whereas the remainder associated up to eight. Age‐at‐onset data indicated both pediatric and adult presentations in 43% of genes. Targeted exome reanalysis using a 220‐gene list identified 37 clinically relevant variants across 28 genes, resolving 16 cases and increasing diagnostic yield by 0.4%. Conclusions: This study offers a systematic framework for designing a unified MD panel by integrating evidence from multiple sources and accounting for phenotypic and age heterogeneity. Targeted reanalysis yielded actionable diagnoses, confirming its benefit in routine clinical practice. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Duchenne/Becker muscular dystrophy (DMD/BMD) is associated with a wide spectrum of brain-related comorbidities. Methods: This retrospective study assesses the neuropsychiatric profile of DMD/BMD patients and the hypothesis of a functional-versus-structural approach of dystrophin gene variants/impaired isoforms in relation to brain comorbidities. Patients with documented mutation in the DMD gene and neuropsychiatric assessments were included. Seven comorbidities were analyzed based on variant location and dystrophin brain isoform disruption. The clustering of comorbidities and genotype–phenotype correlations were studied. Results: 264 DMD/BMD patients met inclusion criteria. 22 variants have never been described before. A high prevalence of neuropsychiatric comorbidities was identified in the cohort with higher values in patients with distal mutations. The number of comorbidities increased with the number of brain dystrophin isoforms predicted to be lost. Functional-versus-structural comparison revealed that Dp140 5′UTR variants might not affect protein expression. Epilepsy and intellectual disability (ID) showed significant association in this cohort. Neuropsychiatric phenotype varied greatly in patients with identical variants, even between siblings. Conclusions: This is one of the largest European cohorts for which all these comorbidities were studied in association with DMD gene mutation site and the first study of this kind performed on the Eastern European DMD/BMD population. Our group analyzed, for the first time, Dp140 5′UTR variants in relation to all neuropsychiatric phenotypes and showed that epilepsy and ID are strongly associated in DMD/DMB patients.