Mitochondrial complex I NUBPL mutations cause combined dystonia with bilateral striatal necrosis and cerebellar atrophy
Mitochondrial complex I NUBPL mutations cause combined dystonia with bilateral striatal necrosis and cerebellar atrophy
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DOI：
10.1111/ene.13956
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发表时间：
2019-09-01
影响因子：
5.1
通讯作者：
Bhatia, K. P.
中科院分区：
文献类型：
--
作者：
Balint, B.;Charlesworth, G.;Bhatia, K. P.
背景与目的遗传学的最新进展有助于阐明许多肌张力障碍综合征的病因。随着遗传学定义的肌张力障碍综合征范围的扩大，不同的临床放射学表型是指导诊断工作的一个受欢迎的手柄。方法采用外显子组测序技术，对1例以广泛性肌张力障碍、锥体和小脑受累、双侧纹状体坏死（BSN）和小脑萎缩为特征的MRI表现的综合征进行遗传学分析。纯合性作图和连锁分析被用于支持的作用。通过使用外显子组数据或桑格测序排除BSN的已知遗传原因。结果在一个小的UK家系中发现NUBPL基因的复合杂合突变。该基因位于一个正连锁区域，在一个6人的家系中与疾病分离。结论NUBPL基因突变可导致早发性、常染色体隐性遗传性全身性肌张力障碍伴小脑共济失调、锥体束征、认知功能保留、BSN和小脑萎缩的MRI表现。
Background and purpose The recent advances in genetics have helped to unravel the cause of many dystonia syndromes. With the broadening spectrum of genetically defined dystonia syndromes, distinct clinico-radiological phenotypes are a welcome handle to guide the diagnostic work-up. Methods Exome sequencing was used to elucidate the genetic cause of a syndrome characterized by generalized dystonia, pyramidal and cerebellar involvement, with bilateral striatal necrosis (BSN) and cerebellar atrophy on magnetic resonance imaging. Homozygosity mapping and linkage analysis were used in a supportive role. Known genetic causes of BSN were excluded by use of exome data or Sanger sequencing. Results Compound heterozygous mutations were identified in the NUBPL gene in a small UK kindred. The gene lay in a region of positive linkage and segregated with disease in a family of six individuals. Conclusion NUBPL mutations cause early onset, autosomal recessive generalized dystonia with cerebellar ataxia, pyramidal signs, preserved cognition and a distinct magnetic resonance imaging appearance with BSN and cerebellar atrophy.