Program

Oral Sessions

Day 4, May 18（Fri.）　15:25-15:45　Room B (Seiun 1)

4B-O2-P-1525　　PDF

Identification of pathogenic mutations in patients with rare diseases using multiomics approaches

(Nagoya Univ.)
^oYasuyoshi Oka, Tomoo Ogi

DNA damage response and DNA repair system are prerequisite for the maintenance of genome stability. Mutations in genes encoding many components of DNA damage response and DNA repair can result in a number of genetic disorders, “genomic instability syndromes” with congenital developmental abnormalities, neurodegenerative disorders, premature aging, and so forth. Recent extensive studies using next-generation sequencing analysis identify pathogenic mutations in patients with genomic instability. Because the average healthy person has dozens of genetic variants predicted to severely disrupt protein-coding genes, known as loss-of-function variants, and whole-exome sequencing is not able to detect chromosomal translocations, large chromosomal deletions, non-canonical splicing mutations and abnormal regulatory elements, it is difficult to narrow down and identify pathogenic mutations from patients with extremely rare genetic diseases using only next-generation sequencing technologies. Using a deep proteome analysis and whole-genome sequencing, we found the novel disease-causing mutation in a DNA metabolism gene from the patient with microcephaly, cerebral atrophy, and basal ganglia calcification, who was undiagnosed using a single whole-exome sequencing analysis. Multiomics approaches would be a powerful strategy to identify pathogenic mutations in patients with rare genetic diseases.