CEP89 – Intellectual Disability

In a cohort of 5,531 patients with intellectual disability/multiple congenital anomalies (ID/MCA), high-resolution SNP array screening identified 1,663 rare copy-number variants, including 437 de novo events and 638 inherited events, uncovering 20 de novo single-gene CNVs implicating novel ID/MCA genes (PMID:24038936). Among these, a de novo heterozygous CNV encompassing CEP89 suggests haploinsufficiency as a disease mechanism for intellectual disability (PMID:24038936).

Currently, only a single de novo CNV in CEP89 has been reported without segregation or functional follow-up, limiting the strength of this association to Limited under ClinGen criteria. No missense, truncating, or other sequence-level variants have been described, and no experimental models or assays have been performed to date.

Key take-home: CEP89 haploinsufficiency is a candidate cause of autosomal dominant intellectual disability, but additional case and functional data are required to confirm clinical validity.

References

• Human Mutation • 2013 • Clinical significance of de novo and inherited copy-number variation. PMID:24038936

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