CEP19 – Bardet–Biedl syndrome

In a single consanguineous family (PMID:29127258), autosomal recessive Bardet–Biedl syndrome was associated with a homozygous truncating CEP19 variant, c.182dup (p.Tyr61Ter), identified by linkage analysis and exome sequencing. Affected individuals exhibited postaxial polydactyly, rod–cone dystrophy, obesity, intellectual disability, renal malformations, dental anomalies, developmental delay, and speech disorders. Variants in GLI1 and known modifier alleles in CCDC28B and other BBS genes co-segregated but the CEP19 loss-of-function variant perfectly tracked the core phenotype. The c.182dup (p.Tyr61Ter) change introduces a premature stop codon consistent with haploinsufficiency of this centrosomal and ciliary protein. In silico modelling predicts a deleterious structural impact on CEP19. No additional functional assays have yet been reported. Although the evidence is limited to a single kindred, robust segregation and phenotypic concordance support a likely pathogenic role for CEP19 in Bardet–Biedl syndrome.

Key Take-home: CEP19 truncating variants warrant inclusion in diagnostic panels for autosomal recessive Bardet–Biedl syndrome.

References

• Journal of medical genetics • 2018 • Homozygous mutation in CEP19, a gene mutated in morbid obesity, in Bardet-Biedl syndrome with predominant postaxial polydactyly. PMID:29127258

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