Autosomal Recessive Rod–Cone Dystrophy with Mild Extra-Ocular Manifestations Due to a Splice-Affecting Variant in BBS9

Iris Deitch, Sofia Itskov, Daan Panneman, Aasem Abu Shtaya, Tal Saban, Yael Goldberg, Miriam Ehrenberg, Frans P.M. Cremers, Susanne Roosing, Tamar Ben-Yosef*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Bardet–Biedl syndrome (BBS), one of the most common forms of syndromic inherited retinal diseases (IRDs), is characterized by the combination of retinal degeneration with additional extra-ocular manifestations, including obesity, intellectual disability, kidney disease, polydactyly and other skeletal abnormalities. We observed an Israeli patient with autosomal recessive apparently non-syndromic rod–cone dystrophy (RCD). Extra-ocular findings were limited to epilepsy and dental problems. Genetic analysis with a single molecule molecular inversion probes-based panel that targets the exons and splice sites of 113 genes associated with retinitis pigmentosa and Leber congenital amaurosis revealed a homozygous rare missense variant in the BBS9 gene (c.263C>T;p.(Ser88Leu)). This variant, which affects a highly conserved amino acid, is also located in the last base of Exon 3, and predicted to be splice-altering. An in vitro minigene splice assay demonstrated that this variant leads to the partial aberrant splicing of Exon 3. Therefore, we suggest that this variant is likely hypomorphic. This is in agreement with the relatively mild phenotype observed in the patient. Hence, the findings in our study expand the phenotypic spectrum associated with BBS9 variants and indicate that variants in this gene should be considered not only in BBS patients but also in individuals with non-syndromic IRD or IRD with very mild extra-ocular manifestations.

Original languageEnglish
Pages (from-to)2566-2575
Number of pages10
JournalCurrent Issues in Molecular Biology
Issue number3
StatePublished - Mar 2024


FundersFunder number
Sisenwein Research Fund
Ministry of Health, State of Israel3-18611


    • BBS9
    • Bardet–Biedl syndrome
    • retina
    • retinitis pigmentosa
    • rod–cone dystrophy


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