CDH15 – Intellectual Disability

Autosomal dominant disruption of CDH15 has been reported in five unrelated individuals with intellectual disability, including one patient with a de novo t(11;16) translocation and four probands carrying rare CDH15 missense alleles, absent in over 800 controls and 600 additional ID cases ([PMID:19012874]). Three of these variants—c.178C>T (p.Arg60Cys), c.274C>T (p.Arg92Trp), and c.365C>T (p.Ala122Val)—alter highly conserved residues within the extracellular cadherin repeats. No familial segregation data are available, and no recurrent or founder variants have been documented, yielding limited genetic evidence for causality.

In vivo expression studies demonstrate that three CDH15 missense variants impair cadherin-mediated cell–cell adhesion in Xenopus embryos, supporting a loss-of-function mechanism ([PMID:19012874]). No animal models or rescue experiments have been reported. Taken together, the current data provide biologic plausibility but insufficient genetic validation for a definitive relationship. Key take-home: CDH15 disruption shows a limited yet functionally supported association with autosomal dominant intellectual disability, meriting further clinical and genetic investigation.

References

• American Journal of Human Genetics • 2008 • Alterations in CDH15 and KIRREL3 in patients with mild to severe intellectual disability. PMID:19012874

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