Detection of rare genetic variations in the promoter regions of the ATG16L gene in Parkinson's patients.

Mutations in the ATG genes have been related to impair autophagic function, contributing to the sporadic onset of Parkinsońs Disease (PD). However, scarce studies have been performed about ins/del within the regulatory domains of the autophagy genes in sporadic PD patients. This study was aimed to found ins/del within part of the crucial core autophagy promotor gene region of the ATG16L1 in a groups of sporadic PD patients. After developing a genetic marker to find ins/del using fragment size analysis, a rare mutation by insertion (0.45%) was reported in the patients. This mutation was characterized by sequencing. No others ins/del were found. As a results, the frequency of this insertion should be considered as a rare genetic variant. An in silico analysis also highlighting the usefulness of a search GDV which revealed multiples ins/del within ATG16L1 promoter. Furthermore, these genetic insertions could be found in patients with sporadic PD in the ATG161L promoter gene. When a breakpoint as deletions, insertions or tandem duplication are located within a functional gene interruption of the gene and a loss of function was expected but removing or altering in the regulatory sequence can influence the expression or the regulation of a nearby gene which may impair healthy due to dosage effects in sporadic diseases.