Four genes associated with isolated dystonia are currently well replicated and validated. DYT-THAP1 manifests as young-onset generalized dystonia with predominant craniocervical symptoms; and is associated with mostly deleterious missense variation in the THAP1 gene. De novo and inherited missense and protein truncating variation in GNAL as well as primarily missense variation in ANO3 cause isolated focal and/or segmental dystonia with preference for the upper half of the body and older ages at onset. The GAG deletion in TOR1A is associated with generalized dystonia with onset in childhood in the lower limbs. Rare variation in these genes causes monogenic sporadic and inherited forms of isolated dystonia; common variation may confer risk and imply that dystonia is a polygenic trait in a subset of cases. Although candidate gene screens have been successful in the past in detecting gene-disease associations, recent application of whole-genome and whole-exome sequencing methods enable unbiased capture of all genetic variation that may explain the phenotype. However, careful variant-level evaluation is necessary in every case, even in genes that have previously been associated with disease. We review the genetic architecture and phenotype of DYT-THAP1, DYT-GNAL, DYT-ANO3, and DYT-TOR1A by collecting case reports from the literature and performing variant classification using pathogenicity criteria.

四个与孤立性肌张力障碍相关的基因目前已得到很好的复制和验证。DYT - THAP1表现为以颅颈症状为主的年轻全身性肌张力障碍；并且主要与THAP1基因中的有害错义变异相关。从头和遗传错义和蛋白截断变异GNAL如以及主要错义变异ANO3原因分离焦和/或节段性张力障碍与偏爱身体的上半部分和较大年龄发病。TOR1A 中的 GAG 缺失与儿童下肢的全身性肌张力障碍有关。这些基因的罕见变异导致单基因散发和遗传形式的孤立性肌张力障碍；常见变异可能会带来风险，并暗示肌张力障碍是部分病例的多基因特征。尽管过去候选基因筛选在检测基因-疾病关联方面取得了成功，但最近全基因组和全外显子组测序方法的应用能够无偏见地捕获所有可能解释表型的遗传变异。然而，在每种情况下都需要仔细的变异水平评估，即使在以前与疾病相关的基因中也是如此。我们回顾了 DYT- THAP1、DYT- GNAL、DYT- ANO3和 DYT-的遗传结构和表型TOR1A通过从文献中收集病例报告并使用致病性标准进行变异分类。