The SIRT2 gene encodes an enzyme that is responsible for the NAD-dependent deacetylation of histones and alpha-tubulin. The enzyme is thus involved in several cellular processes such as autophagy, lipid and protein catabolism, transcription, chromatin and gene silencing, the meiotic cell cycle and cell proliferation. It is responsible for the cellular response to oxidative stress, hypoxia, caloric restriction, epinephrine stimulus, hepatocyte growth factor stimulus and molecules of bacterial origin. SIRT2 also plays a role in striated muscle tissue development, myelination in the peripheral nervous system during postnatal development and remyelination post-injury.
The SIRT2 gene is located on the long arm of chromosome 19. It spans a length of 21.3 kb of DNA and its coding sequence is spread across 17 exons. The gene encodes a 43 kDa protein product comprised of 389 amino acids. Several isoforms of the SIRT2 protein exist due to alternatively spliced transcript variants. The gene is widely expressed in the human body with high expression seen in the brain, spinal cord, heart and skeletal muscle.
Monies et al. (2017) reported the findings of 1000 diagnostic panels and exomes carried out at a next generation sequencing lab in Saudi Arabia. One patient, a 1-year-old female from a consanguineous family, presented with microcephaly, fine/gross motor delay, speech delay, learning disability, developmental regression, periventricular leukomalacia, prematurity, oligohydramnios, nystagmus and recurrent fever. Whole exome sequencing helped identify a homozygous mutation (c.70G>T, p.E24X) in exon 3 of the patient’s SIRT2 gene. This gene mutation was considered a candidate for pathogenicity as it was a novel variant located within the autozygome and was predicted to be deleterious; and the gene had been implicated in myelination. The authors noted the need for independent confirmation of this association.