TRIM32 – Bardet-Biedl syndrome

TRIM32 is one of the 12 genes implicated in Bardet-Biedl syndrome (BBS), a rare autosomal recessive ciliopathy characterized by retinal dystrophy, postaxial polydactyly, obesity, hypogonadism, intellectual disability and renal/hepatic involvement. Pathogenic variants in TRIM32 were identified in three unrelated BBS probands, including one sporadic case and a pair of affected siblings, confirming autosomal recessive inheritance and providing preliminary segregation data (3 probands total; 2 sibs) ([PMID:18319026], [PMID:25960897]). Clinical features across these cases consistently included obesity (HP:0001513), postaxial polydactyly (HP:0010442), hypogonadism (HP:0000135), retinal dystrophy (HP:0000556) and intellectual disability (HP:0001249).

Functional studies of TRIM32 reveal domain-specific effects: mutations in the NHL repeats disrupt ubiquitin ligase activity linked to limb-girdle muscular dystrophy, whereas a distinct B-box domain alteration underlying BBS11 retains self-interaction but likely perturbs non-muscle pathways ([PMID:17994549]). However, no dedicated cellular or animal models have yet recapitulated BBS-associated TRIM32 defects. Overall, genetic evidence is limited by small case numbers and partial segregation, and experimental data in BBS context remain sparse. Key take-home: TRIM32 should be considered in genetic testing panels for BBS, with recognition that additional functional validation is needed to fully establish its mechanistic role and inform clinical management.

References

• Dermatology online journal • 2008 • Bardet-Biedl syndrome: a case report. PMID:18319026
• Case reports in nephrology • 2015 • Two brothers with bardet-biedl syndrome presenting with chronic renal failure. PMID:25960897
• Human mutation • 2008 • Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H. PMID:17994549

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