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<p>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 (<i>n</i> = 153 affected individuals [<i>n</i> = 152 index cases from 152 dystonia families], <i>n</i> = 10 unaffected family members). Pathogenic or likely pathogenic variants were identified in established (<i>n</i> = 7) and less-established (<i>n</i> = 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.</p>

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Genetic assessment of consecutively recruited dystonia cases from a single center

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月22日

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  • Burcu Atasu,
  • Javier Simón-Sánchez,
  • Ann-Kathrin Hauser,
  • Peter Heutink,
  • Thomas Gasser,
  • Ebba Lohmann

摘要

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.