PDF(Pubmed)
Abstract：
UNASSIGNED: Dystonia is a genetic or non-genetic movement disorder with typical patterned and twisting movements due to abnormal muscle contractions that may be associated with tremor. Genetic and phenotypic heterogeneity leads to variable clinical presentation.
UNASSIGNED: Next-generation sequencing technologies are being currently used in the workup of patients with inherited dystonia to determine the specific cause in the individuals with autosomal dominant, recessive, X-linked or mitochondrial inheritance patterns. Calcium voltage-gated channel subunit alpha1 A (CACNA1A) gene variants are rare in dystonias.
UNASSIGNED: We here present a 20-year-old man with a history of delayed milestones, flexor posturing, dysarthria, dysphagia and a negative family history from consanguineous parents. Neurological examination revealed right lateral scoliosis of the neck and generalised dystonic posturing affecting both upper and lower limbs. MRI of the brain was unremarkable. Molecular genetic results revealed a heterozygous variant in the CACNA1A gene (CHR19: NM_023035.2, c. 1602G>A; p. Met534Ile). Segregation analyses in both the parents revealed wild-type CACNA1A gene suggesting de novo nature of the variant with a likely pathogenic classification.
UNASSIGNED: Dystonia is one of the clinical phenotypes that can be associated with CACNA1A gene mutations and we recommend that this gene either be included in the dystonia panel offered or tested when the initial primary genetic result is negative.
UNASSIGNED: Next-generation sequencing technologies are being currently used in the workup of patients with inherited dystonia to determine the specific cause in the individuals with autosomal dominant, recessive, X-linked or mitochondrial inheritance patterns. Calcium voltage-gated channel subunit alpha1 A (CACNA1A) gene variants are rare in dystonias.
UNASSIGNED: We here present a 20-year-old man with a history of delayed milestones, flexor posturing, dysarthria, dysphagia and a negative family history from consanguineous parents. Neurological examination revealed right lateral scoliosis of the neck and generalised dystonic posturing affecting both upper and lower limbs. MRI of the brain was unremarkable. Molecular genetic results revealed a heterozygous variant in the CACNA1A gene (CHR19: NM_023035.2, c. 1602G>A; p. Met534Ile). Segregation analyses in both the parents revealed wild-type CACNA1A gene suggesting de novo nature of the variant with a likely pathogenic classification.
UNASSIGNED: Dystonia is one of the clinical phenotypes that can be associated with CACNA1A gene mutations and we recommend that this gene either be included in the dystonia panel offered or tested when the initial primary genetic result is negative.
摘要：
■肌张力障碍是一种遗传性或非遗传性运动障碍，由于可能与震颤有关的异常肌肉收缩而具有典型的模式化和扭曲运动。遗传和表型异质性导致不同的临床表现。
■下一代测序技术目前正在用于遗传性肌张力障碍患者的检查，以确定常染色体显性遗传个体的具体原因。隐性,X连锁或线粒体遗传模式。钙电压门控通道亚基α1A（CACNA1A）基因变体在肌张力障碍中很少见。
■我们在这里介绍一个20岁的男人，他有延迟的里程碑历史，flexor姿势，构音障碍,吞咽困难和亲缘父母的阴性家族史。神经系统检查显示，颈部右侧脊柱侧弯和全身肌张力障碍姿势影响上肢和下肢。脑部MRI无异常。分子遗传学结果揭示了CACNA1A基因中的杂合变体(CHR19:NM_023035.2,c.1602G>A;p.Met534Ile)。父母双方的分离分析均显示野生型CACNA1A基因，表明该变体的从头性质具有可能的致病性分类。
肌张力障碍是可能与CACNA1A基因突变相关的临床表型之一，我们建议将该基因包括在所提供的肌张力障碍组中，或在初始遗传结果为阴性时进行测试。
■下一代测序技术目前正在用于遗传性肌张力障碍患者的检查，以确定常染色体显性遗传个体的具体原因。隐性,X连锁或线粒体遗传模式。钙电压门控通道亚基α1A（CACNA1A）基因变体在肌张力障碍中很少见。
■我们在这里介绍一个20岁的男人，他有延迟的里程碑历史，flexor姿势，构音障碍,吞咽困难和亲缘父母的阴性家族史。神经系统检查显示，颈部右侧脊柱侧弯和全身肌张力障碍姿势影响上肢和下肢。脑部MRI无异常。分子遗传学结果揭示了CACNA1A基因中的杂合变体(CHR19:NM_023035.2,c.1602G>A;p.Met534Ile)。父母双方的分离分析均显示野生型CACNA1A基因，表明该变体的从头性质具有可能的致病性分类。
肌张力障碍是可能与CACNA1A基因突变相关的临床表型之一，我们建议将该基因包括在所提供的肌张力障碍组中，或在初始遗传结果为阴性时进行测试。
