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CTTNBP2 – Autism Spectrum Disorder

A de novo heterozygous CTTNBP2 p.Met115Thr variant was identified in a quad family by whole-exome sequencing in a child with autism spectrum disorder, with no clinically significant copy number variants detected ([PMID:36670631]). This represents a single unrelated proband observation supporting a limited genetic association, with no additional affected relatives or segregation data reported.

Functional studies of ASD-linked CTTNBP2 mutations reveal mechanistic deficits in dendritic spine formation. In cultured neurons, M120I, R533Ter, and Asp570Tyr variants impair cortactin interactions or mislocalize CTTNBP2, reducing spine density. A heterozygous M120I knock-in mouse model recapitulates reduced social interaction and spine abnormalities, supporting a role for haploinsufficiency in ASD pathogenesis ([PMID:33168105]).

CTTNBP2 de novo variants constitute candidate risk alleles for ASD with preliminary functional support; further replication and segregation studies are needed to establish diagnostic utility.

References

  • Children (Basel, Switzerland) • 2022 • Dendritic Spine in Autism Genetics: Whole-Exome Sequencing Identifying De Novo Variant of CTTNBP2 in a Quad Family Affected by Autism Spectrum Disorder PMID:36670631
  • Acta neuropathologica communications • 2020 • Autism-linked mutations of CTTNBP2 reduce social interaction and impair dendritic spine formation via diverse mechanisms PMID:33168105

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Single de novo proband observed (n=1) with CTTNBP2 p.Met115Thr in ASD ([PMID:36670631]); no familial segregation

Genetic Evidence

Limited

One unrelated quad family proband with de novo CTTNBP2 variant; no additional segregation data

Functional Evidence

Moderate

Knock-in M120I mouse model shows ASD-like social deficits and dendritic spine pathology, and cellular assays demonstrate spine density reduction ([PMID:33168105])