CLN8 – Autism Spectrum Disorder

CLN8 c.71G>A (p.Arg24His) was identified by whole‐exome sequencing in one Japanese multiplex family, co-segregating with ASD in three affected siblings and their affected father (3 probands, 1 relative) (PMID:25806950). In a two-stage follow-up case-control study (Niigata: 241 patients/667 controls; Nagoya: 309 patients/350 controls), this variant showed no significant association (odds ratio=1.8, 95% CI=0.1–29.6) (PMID:25806950). A separate resequencing in 256 ASD patients and association analysis in 568 patients/1 017 controls found no significant link for five rare missense variants—including p.Arg24His, p.Phe39Leu, p.Arg97His, p.Thr108Met, p.Asn152Ser—between CLN8 and ASD (PMID:26657971). Overall, segregation in a single family without replication in larger cohorts supports a Limited association. No functional studies address CLN8 variants in ASD. Additional large-scale and functional investigations are required. Key Take-home: Current evidence does not support clinical testing of CLN8 for ASD risk.

References

• PloS one • 2015 • Novel rare missense variations and risk of autism spectrum disorder: whole-exome sequencing in two families with affected siblings and a two-stage follow-up study in a Japanese population. PMID:25806950
• PloS one • 2015 • Resequencing and Association Analysis of CLN8 with Autism Spectrum Disorder in a Japanese Population. PMID:26657971

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