CAPRIN1 – Autism Spectrum Disorder

CAPRIN1 encodes an RNA‐binding protein critical for dendritic mRNA transport and neuronal network formation. A heterozygous CAPRIN1 mutation was identified in one ASD proband ([PMID:26865403]), and whole-genome sequencing of 32 ASD families detected a rare CAPRIN1 variant in one additional family ([PMID:23849776]). To date, no extended familial segregation data have been reported, and the human genetic evidence remains limited.

Autosomal dominant inheritance is suggested by heterozygous variants. Rng105(+/–) mice, modeling CAPRIN1 haploinsufficiency, exhibit reduced social interaction, weak preference for social and object novelty, and impaired reversal learning—behaviors analogous to ASD core features ([PMID:26865403]). An oligogenic contribution is further supported by the nonrandom co-occurrence of CAPRIN1 de novo variants with other extreme DNVs in ASD trios ([PMID:31332282]). No studies dispute this association.

Collectively, CAPRIN1 shows limited genetic evidence in humans but moderate functional support from animal models. Additional human studies are warranted to establish variant pathogenicity and inform clinical testing. Key Take-home: CAPRIN1 haploinsufficiency may contribute to ASD risk, but clinical interpretation requires further validation.

References

• Scientific reports • 2016 • Comprehensive behavioral analysis of RNG105 (Caprin1) heterozygous mice: Reduced social interaction and attenuated response to novelty. PMID:26865403
• American journal of human genetics • 2013 • Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing. PMID:23849776
• Genetics in medicine : official journal of the American College of Medical Genetics • 2020 • Nonrandom occurrence of multiple de novo coding variants in a proband indicates the existence of an oligogenic model in autism. PMID:31332282

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