Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
Mov Disord. 2012 May;27(6):789-93. doi: 10.1002/mds.24980. Epub 2012 Apr 16.
Neurodegeneration with brain iron accumulation is clinically and genetically heterogeneous because of mutations in at least 7 nuclear genes.
We performed homozygosity mapping and whole-exome sequencing in 2 brothers with brain iron accumulation from a consanguineous family.
We identified a homozygous missense mutation in both brothers in the very recently identified chromosome 19 open-reading frame 12 gene. The disease presented before age 10 with slowly progressive tremor, dystonia, and spasticity. Additional features were optic atrophy, peripheral neuropathy, and learning difficulties. A raised serum creatine kinase indicated neuromuscular involvement, and compensatory mitochondrial proliferation implicated mitochondrial dysfunction as a pathological mechanism.
Further studies are needed to explore the function of the chromosome 19 open-reading frame 12 gene, and extended genetic analysis on larger patient cohorts will provide more information about the presentation and frequency of this disease.
脑铁蓄积性神经退行性变由于至少 7 个核基因突变，在临床上和遗传学上存在异质性。
我们对来自一个近亲家庭的 2 名脑铁蓄积兄弟进行了纯合子作图和全外显子组测序。
我们在这 2 名兄弟中均发现了一个非常新发现的染色体 19 开放阅读框 12 基因的纯合错义突变。该疾病在 10 岁之前表现为进行性震颤、肌张力障碍和痉挛。其他特征包括视神经萎缩、周围神经病和学习困难。血清肌酸激酶升高提示存在神经肌肉受累，而代偿性线粒体增生提示线粒体功能障碍是一种病理机制。
需要进一步研究染色体 19 开放阅读框 12 基因的功能，对更大的患者队列进行扩展的遗传分析将提供更多关于该疾病表现和频率的信息。
