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CEP290 – Bardet-Biedl syndrome

Bardet-Biedl syndrome (BBS) is an autosomal recessive multisystem ciliopathy characterized by rod-cone dystrophy, postaxial polydactyly, obesity, intellectual disability and renal anomalies. Mutations in at least 21 genes underlie BBS; CEP290 (HGNC:29021) has been implicated in a subset of patients presenting classic BBS features, including two affected siblings with renal failure ((PMID:25960897)) and an unrelated family harboring a homozygous truncating variant c.5704G>T (p.Glu1902Ter) segregating with disease ((PMID:18327255)).

CEP290 encodes a centrosomal protein localized to the ciliary transition zone, where it interacts with PCM-1 and is required for ciliogenesis. Loss-of-function variants disrupt cilium formation and phenocopy BBS gene defects, consistent with a recessive mechanism ((PMID:18772192)).

Key take-home: Biallelic CEP290 truncating variants cause autosomal recessive Bardet-Biedl syndrome by abrogating transition-zone function and ciliogenesis, supporting its inclusion in diagnostic panels for BBS.

References

  • Case reports in nephrology • 2015 • Two brothers with bardet-biedl syndrome presenting with chronic renal failure. PMID:25960897
  • Nature genetics • 2008 • Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome. PMID:18327255
  • Human molecular genetics • 2008 • CEP290 interacts with the centriolar satellite component PCM-1 and is required for Rab8 localization to the primary cilium. PMID:18772192

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Three affected individuals across two families (two siblings and one independent kindred) with homozygous truncating CEP290 variants segregating under AR inheritance

Genetic Evidence

Limited

One homozygous truncating variant (c.5704G>T) segregated in an unrelated BBS family (PMID:18327255); two sibling cases reported without specific CEP290 variants (PMID:25960897)

Functional Evidence

Moderate

CEP290 localizes to the ciliary transition zone, interacts with PCM-1 and is essential for ciliogenesis, supporting a loss-of-function mechanism in BBS (PMID:18772192)