Copy number variation of LINGO1 in familial dystonic tremor
Copy number variation of LINGO1 in familial dystonic tremor
复制标题
DOI：
10.1212/nxg.0000000000000307
复制
发表时间：
2019-02-01
影响因子：
3.1
通讯作者：
Crosby, Andrew H.
中科院分区：
文献类型：
--
作者：
Alakbarzade, Vafa;Iype, Thomas;Crosby, Andrew H.
目的阐明一个5代南印度家系的遗传原因，该家系有多个以上肢姿势性震颤和与另一种形式的震颤（即张力障碍性震颤）一致的姿势的个体。方法采用全基因组单核苷酸多态性（SNP）基因芯片分析方法，在受影响的个体中寻找拷贝数变异。结果全基因组SNP微阵列分析发现，所有受影响的家族成员均存在染色体15 q24的串联重复基因组片段。全基因组测序表明，它包括一个类似的550-kb的串联重复，包括整个LINGO 1基因。结论基因组重复作为这种情况的可能分子原因的鉴定，导致在受影响的情况下，额外的LINGO 1基因拷贝，进一步支持该基因在震颤疾病中的因果作用，并暗示LINGO 1的表达水平增加作为一种潜在的致病机制。
Objective To elucidate the genetic cause of a large 5 generation South Indian family with multiple individuals with predominantly an upper limb postural tremor and posturing in keeping with another form of tremor, namely, dystonic tremor. Methods Whole-genome single nucleotide polymorphism (SNP) microarray analysis was undertaken to look for copy number variants in the affected individuals. Results Whole-genome SNP microarray studies identified a tandem duplicated genomic segment of chromosome 15q24 present in all affected family members. Whole-genome sequencing demonstrated that it comprised a similar to 550-kb tandem duplication encompassing the entire LINGO1 gene. Conclusions The identification of a genomic duplication as the likely molecular cause of this condition, resulting in an additional LINGO1 gene copy in affected cases, adds further support for a causal role of this gene in tremor disorders and implicates increased expression levels of LINGO1 as a potential pathogenic mechanism.