Hadi Abdul Fuad, Arta Reza K, Kushima Itaru, Egawa Jun, Watanabe Yuichiro, Ozaki Norio, Someya Toshiyuki
Department of Psychiatry, School of Medicine, and Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Neuropsychopharmacol Rep. 2025 Mar;45(1):e12527. doi: 10.1002/npr2.12527.
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.
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.
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.
This study does not provide evidence for the contribution of rare CNTN5 variants to the genetic etiology of ASD in the Japanese population.
Contactin-5（CNTN5）是一种参与听觉通路突触形成和突触成熟的神经粘附分子，与自闭症谱系障碍（ASD）的病理生理学有关，尤其是听觉过敏。为了研究罕见的CNTN5变异在ASD易感性中的作用，我们在日本人群中进行了重测序和关联分析。
我们对302例ASD患者的CNTN5编码区进行了重测序，并对罕见的可能有害变异进行了优先级排序。然后，对313例ASD患者和1065例对照进行了优先级变异的基因分型。随后，我们在614例ASD患者和61057例对照中对选定变异与ASD进行了关联研究。对携带优先级变异的患者的临床数据进行了回顾。
通过重测序，我们在ASD患者中确定了三个罕见的可能有害的错义变异（W69G、I227L和L1000S）。虽然我们发现I227L变异与ASD之间存在名义上的显著关联，但在事后校正后并不显著。在携带优先级变异的9例患者中，有3例出现听觉过敏。
本研究没有提供证据表明罕见的CNTN5变异对日本人群ASD的遗传病因有贡献。
