Deletions in OPTN gene and literature review

Abstract

Amyotrophic lateral sclerosis 12 with or without frontotemporal dementia (ALS12) is a subtype of ALS that is a neurodegenerative disorder onset in adulthood and is characterized by slowly progressive. The ALS12 is caused by a heterozygous or homozygous mutation in the Optineurin gene (OPTN) on chromosome 10p13. In this study, whole genome sequencing (WGS), utilizing next-generation sequencing techniques was performed to identify genes associated with ALS in the patient. These technologies utilize high-throughput DNA sequencing of the whole genome, representing a highly effective approach to the assessment of neurodegenerative disorders. Optical Genomic Mapping (OGM) is a new cytogenomics technics has taken the technology to the next level in the cytogenetics field by enabling the mapping of all types of structural variants (SVs) at high resolution in a single assay. It has become a prominent diagnosis method in neurogenetics and other disciplines in recent years with its ability to analyze variants that other technologies cannot detect by reaching high-resolution values that other technologies cannot reach, by using long read and specific labeling methods. In this study, we found the novel homozygous OPTN gene deletion by OGM in a patient with diagnosed ALS12 and confirmed and detected precise deletion breakpoints by WGS. We aimed to explore the utility of OGM and WGS as a method of characterizing the SVs associated with the Alu-mediated rearrangement.