A compound heterozygous missense mutation and a large deletion in the KCTD7 gene presenting as an opsoclonus-myoclonus ataxia-like syndrome
A compound heterozygous missense mutation and a large deletion in the KCTD7 gene presenting as an opsoclonus-myoclonus ataxia-like syndrome
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DOI：
10.1007/s00415-012-6545-z
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发表时间：
2012-12-01
影响因子：
6
通讯作者：
Leshinsky-Silver, Esther
中科院分区：
文献类型：
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作者：
Blumkin, Lubov;Kivity, Sara;Leshinsky-Silver, Esther
到目前为止，在一个进行性肌阵挛癫痫家系中描述了钾通道相关基因KCTD7的突变。我们描述了一种独特的表型：急性发作的肌阵挛和共济失调，伴随着异常的视阵挛样眼球运动；临床症状在类固醇治疗下得到改善；两年后出现癫痫活动，但没有明显的癫痫发作。排除可能的遗传原因后，进行全基因组外显子组测序，以确定致病基因。外显子测序检测到1个杂合性错义突变(R84W)，MLPA分析发现外显子3和4大量杂合性缺失。父亲为R84W突变杂合子，母亲为外显子3+4缺失杂合子。该突变会影响预测蛋白质的一个高度保守的片段，将碱性氨基酸变为中性。较大的缺失可能导致蛋白质被截断。不同的表型拓宽了KCTD7相关疾病的范围。因此，诊断为眼阵挛-肌阵挛且病程不典型的患者应评估KCTD7突变。
Mutations in the potassium channel-related gene KCTD7 were described so far in a single family with progressive myoclonus epilepsy. We describe a unique phenotype: acute onset of myoclonus and ataxia, associated with abnormal opsoclonus-like eye movements; improvement of clinical symptoms under steroid treatment; and appearance of epileptic activity on EEG 2 years later without overt seizures. After excluding possible genetic causes, whole-genome exome sequencing was performed in order to identify the causative gene. One heterozygous missense mutation (R84W) was detected by exome sequencing and a large heterozygous deletion of exons 3 and 4 by MLPA analysis. The father is heterozygous for the R84W mutation and the mother is heterozygous for the exon 3+4 deletion. The mutation affects a highly conserved segment of the predicted protein, changing a basic amino acid into neutral. The large deletion probably results in a truncated protein. The different phenotype broadens the spectrum of KCTD7-related diseases. Therefore, patients diagnosed as having opsoclonus-myoclonus with an atypical course should be evaluated for KCTD7 mutations.