Genetic assessment of consecutively recruited dystonia cases from a single center

The genetics of dystonia have been extensively investigated in population-based and multicenter cohorts. In this study, we analyzed a consecutively recruited, single-center German dystonia cohort using whole-exome sequencing (n = 153 affected individuals [n = 152 index cases from 152 dystonia families], n = 10 unaffected family members). Pathogenic or likely pathogenic variants were identified in established (n = 7) and less-established (n = 4) dystonia-associated genes, resulting in a diagnostic yield of 7.2% (11/152); all variants were heterozygous. Consistent with previous European studies, earlier age at onset (≤ 40 years; p value = 0.0218) was significantly associated with increased diagnostic yield and demonstrated acceptable predictive value (AUC = 0.76). This study (1) underscores the importance of both shared features-such as clinical characteristics associated with diagnostic yield-and distinct genetic features, including a relatively lower diagnostic rate and differences in the composition of implicated genes across cohort designs, and (2) suggests that exome-based testing may identify clinically relevant variants beyond the classic dystonia genes in selected patients undergoing diagnostic evaluation.