Olfactory Dysfunction in Patients With CNGB1-Associated Retinitis Pigmentosa

Area of Science:

• Genetics
• Neuroscience
• Ophthalmology

Background:

• Retinitis pigmentosa (RP) and olfactory dysfunction can co-occur, suggesting a shared genetic etiology.
• The CNGB1 gene encodes a subunit of a signal transduction channel found in both retinal photoreceptors and olfactory sensory neurons.

Purpose of the Study:

• To investigate olfactory function and retinal characteristics in patients with biallelic mutations in the CNGB1 gene.
• To identify the genetic basis of RP and olfactory dysfunction in affected individuals.

Main Methods:

• A multicenter case series involving 9 patients with CNGB1-associated RP.
• Olfactory testing, ocular phenotyping, and targeted next-generation sequencing for molecular genetic analysis.
• Brain MRI and EEG were performed in one patient to assess olfactory bulb and response.

Main Results:

• All 9 patients exhibited reduced or absent olfactory function, with most scoring in the lowest quartile.
• Retinal examination revealed features consistent with rod-cone dystrophy, often diagnosed later in life due to slow progression.
• Five novel and five previously reported mutations in the CNGB1 gene were identified.

Conclusions:

• Mutations in CNGB1 are associated with an autosomal recessive syndrome combining RP and olfactory dysfunction.
• This syndrome is characterized by slowly progressive retinal degeneration and variable degrees of anosmia or hyposmia.