Abstract
BACKGROUND: Contactin-5 (CNTN5), a neural adhesion molecule involved in synaptogenesis and synaptic maturation in the auditory pathway, has been associated with the pathophysiology of autism spectrum disorder (ASD), particularly hyperacusis. To investigate the role of rare CNTN5 variants in ASD susceptibility, we performed resequencing and association analysis in a Japanese population. METHODS: We resequenced the CNTN5 coding regions in 302 patients with ASD and prioritized rare putatively damaging variants. The prioritized variants were then genotyped in 313 patients with ASD and 1065 controls. Subsequently, we conducted an association study of selected variants with ASD in 614 patients with ASD and 61 057 controls. Clinical data were reviewed for patients carrying prioritized variants. RESULTS: Through resequencing, we prioritized three rare putatively damaging missense variants (W69G, I227L, and L1000S) in patients with ASD. Although we found a nominally significant association between the I227L variant and ASD, it did not remain significant after post hoc correction. Hyperacusis was found in three out of nine patients carrying prioritized variants. CONCLUSION: This study does not provide evidence for the contribution of rare CNTN5 variants to the genetic etiology of ASD in the Japanese population.