BBS2 – Retinitis Pigmentosa

Autosomal recessive variants in BBS2 have been reported in a small number of unrelated patients with retinitis pigmentosa (RP). Three probands were identified with biallelic BBS2 mutations in a cohort of 157 RP families analyzed by exome sequencing (PMID:25999675), and one additional family was found among 76 Chinese RP pedigrees using targeted panel or whole‐exome sequencing (PMID:31960602). The variants include missense and truncating alleles (e.g., c.443A>T (p.Asn148Ile)) with presumed loss‐of‐function effect. No extended segregation beyond the index cases was documented.

Functional knock‐out of Bbs2 in mouse models results in photoreceptor ciliary defects and progressive retinal degeneration recapitulating human RP phenotypes, supporting a loss‐of‐function mechanism (PMID:18032602). There are no conflicting reports disputing this association.

Key Take-home: Although currently supported by a limited number of cases, BBS2 should be considered in autosomal recessive RP diagnostic panels due to concordant in vivo functional evidence.

References

• Molecular vision • 2015 • Mutation analysis in 129 genes associated with other forms of retinal dystrophy in 157 families with retinitis pigmentosa based on exome sequencing. PMID:25999675
• Molecular genetics & genomic medicine • 2020 • Application of targeted panel sequencing and whole exome sequencing for 76 Chinese families with retinitis pigmentosa. PMID:31960602
• Proceedings of the National Academy of Sciences of the United States of America • 2007 • A knockin mouse model of the Bardet-Biedl syndrome 1 M390R mutation has cilia defects, ventriculomegaly, retinopathy, and obesity. PMID:18032602

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