BBS7 – Bardet-Biedl syndrome

Bardet-Biedl syndrome (BBS) is a multisystem autosomal recessive ciliopathy characterised by retinal dystrophy, obesity, polydactyly and renal anomalies. Among the 26 known BBS genes, BBS7 encodes a core subunit of the BBSome complex essential for ciliary membrane trafficking and maintenance. Mutations in BBS7 disrupt BBSome assembly and ciliary function, leading to the pleiotropic features of BBS (PMID:22713813).

Initial linkage and mutation screening in a large Chinese pedigree (19 at-risk individuals) identified a novel homozygous frameshift in BBS7, establishing autosomal recessive inheritance and co-segregation with disease (PMID:19093007). Subsequent exome sequencing in Slavic families revealed a recurrent founder allele, c.1967_1968del (p.Leu656ProfsTer12), in multiple unrelated probands and carriers in the general population (2,832 donors) (PMID:26557828).

Over 20 unrelated probands from diverse ethnicities harbour biallelic BBS7 variants, including nonsense, frameshift, splice-site and missense changes. The mutation spectrum spans LOF alleles (e.g., c.1967_1968del (p.Leu656ProfsTer12)) and hypomorphic missense variants, with recurrence in specific populations (Slavic, Chinese Miao). Deep-intronic and copy-number variants have also been reported, further broadening the allelic diversity.

Segregation data confirm co-segregation of BBS7 variants with disease in multiple families: Chinese pedigree (n=2 affected), Russian kindreds (n=2 affected), Chinese Miao families (n=3 affected) and additional consanguineous cohorts, summing to at least 7 affected relatives with concordant genotypes. Population screening and carrier frequencies support autosomal recessive transmission without significant heterozygote disease risk.

Functional studies demonstrate that BBS7 is integral to the BBSome, required for trafficking of key ciliary cargo; loss-of-function alleles impair ciliogenesis in cellular models and recapitulate retinal and renal phenotypes in animal systems (PMID:22713813). No conflicting evidence or alternative phenotypes have been reported for BBS7 variants in the context of BBS.

References

• Molecular Vision • 2008 • A novel mutation in BBS7 gene causes Bardet-Biedl syndrome in a Chinese family PMID:19093007
• Molecular Syndromology • 2015 • Exome Sequencing of a Family with Bardet-Biedl Syndrome Identifies the Common Russian Mutation c.1967_1968delTAinsC in BBS7 PMID:26557828
• European Journal of Human Genetics • 2013 • Bardet-Biedl syndrome PMID:22713813

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