Copy number variation of LINGO1 in familial dystonic tremor

Abstract

Objective: To elucidate the genetic cause of a large five generation South Indian family with multiple individuals with predomiantly an upper limb postural tremor and posturing in keeping with another form of tremor, namely, dystonic tremor (DT). Methods: Whole genome SNP microarray analysis was undertaken to look for copy number variants (CNVs) 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 ~550kb 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.