CTNND2 – Neurodevelopmental Disorder

Heterozygous CTNND2 exonic deletions and missense variants have been reported in three unrelated individuals with intellectual disability or low-normal IQ with learning difficulties and autism features. One de novo deletion was identified among 714 neurodevelopmental disorder patients (1/714) (PMID:25106414) and two further intragenic deletions were described in isolated intellectual disability (PMID:25839933). Segregation data are limited and no additional familial cases have been reported.

CTNND2 encodes the neuronally expressed δ-catenin protein with predominant expression of two isoforms in rodent brain (PMID:10626844) and interacts postsynaptically with Shank3 via its armadillo repeats, supporting a role in synapse formation (PMID:33115499). These findings suggest haploinsufficiency of CTNND2 as a mechanism underlying neurodevelopmental phenotypes. Key Take-home: CTNND2 haploinsufficiency should be considered in patients with unexplained intellectual disability or autism spectrum features, although evidence remains limited.

References

• Journal of medical genetics • 2014 • The clinical significance of small copy number variants in neurodevelopmental disorders. PMID:25106414
• Gene • 2015 • CTNND2 deletion and intellectual disability. PMID:25839933
• Neuroscience letters • 1999 • Expression of the mRNA for two isoforms of neural plakophilin-related arm-repeat protein/delta-catenin in rodent neurons and glial cells. PMID:10626844
• Molecular autism • 2020 • Targeting of ζ-catenin to postsynaptic sites through interaction with the Shank3 N-terminus. PMID:33115499

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