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Background: The genetics of dystonia have varied across different ethnicities worldwide. Its significance has become more apparent with the advent of deep brain stimulation., Objective: To study the clinico-genetic profile of patients with probable genetic dystonia using whole exome sequencing (WES)., Methods: A prospective, cross-sectional study was conducted from May 2021 to September 2022, enrolling patients with dystonia of presumed genetic etiology for WES. The study compared genetically-determined cases harboring pathogenic/likely-pathogenic variants (P/LP subgroup) with the presumed idiopathic or unsolved cases., Results: We recruited 65 patients (males, 69.2%) whose mean age of onset (AAO) and assessment were 25.0 ± 16.6 and 31.7 ± 15.2 years, respectively. Fifteen had pathogenic/likely-pathogenic variants (yield = 23.1%), 16 (24.6%) had variants of uncertain significance (VUS), 2 were heterozygous carriers while the remaining 32 cases tested negative (presumed idiopathic group). The P/LP subgroup had a significantly younger AAO (16.8 ± 12.3 vs 31.3 ± 17.0 years, p = 0.009), longer duration of illness (10.9 ± 10.3 vs 4.8 ± 4.3 years, p = 0.006), higher prevalence of generalized dystonia (n = 12, 80.0% vs n = 10, 31.3%, p = 0.004), lower-limb onset (n = 5, 33.3% vs n = 1, 3.1%, p = 0.009), higher motor (p = 0.035) and disability scores (p = 0.042). The classical DYT genes with pathogenic/likely pathogenic variants included 3 cases each of TOR1A, and KMT2B, and single cases each of SGCE, EIF2AK2, and VPS16. Non-DYT pathogenic/likely-pathogenic cases included PINK1, PANK2, CTSF, POLG, MICU1, and TSPOAP1., Conclusions: The yield of WES was 23.1% among cases of probable genetic dystonia. Pathogenic or likely pathogenic variants in TOR1A, KMT2B, and SGCE genes were commoner. The absence of family history emphasizes the importance of accurate assessment of clinical predictors before genetic testing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Pantothenate kinase-associated neurodegeneration (PKAN) is the most common "Neurodegeneration with Brain Iron Accumulation" disorder. This study aimed to study the clinical, radiological and genetic profiling of a large cohort of patients with PKAN., Methods: This is an ambispective hospital-based single centre study conducted at a tertiary care centre from India. After tabulating the clinical details, appropriate rating scales were applied followed by magnetic resonance imaging brain and exome sequencing. The segregation of the causal variants in the families were analysed using Sanger sequencing., Results: Twenty-four patients (14 males) with a median age at initial examination of 13 years (range: 4-54 years) and age at onset of 8 years (range: 0.5-40 years) were identified. Almost two-thirds (62%) had onset before 10 years. Difficulty walking was the most common presenting symptom (41.6%) and dystonia was the most common extrapyramidal phenomenology (100%) followed by parkinsonism (54.2%). Retinitis pigmentosa was present in 37.5% patients. MRI showed hypo intensity on T2 and SWI sequences in globus pallidus (100%), substantia nigra (70.8%) and red nucleus (12.5%). Eye-of-the-tiger sign was present in 95.8%. Biallelic variants in PANK2 gene was identified in all 20 patients who underwent genetic testing. Among the 18 unique variants identified in these 20 patients 10 were novel. Sanger sequencing confirmed the segregation of the mutation in the available family members., Conclusions: Wide range of age at onset was noted. Dystonia at presentation, pathognomonic eye-of-tiger sign, and disease-causing variants in PANK2 gene were identified in nearly all patients. Ten novel variants were identified expanding the genotypic spectrum of PKAN., Competing Interests: Declaration of competing interest The authors declares no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)