The CNGB1 gene encodes a protein involved in both photoreceptor and olfactory signal transduction. Patients with retinitis pigmentosa (RP) due to bi-allelic variants in this gene were previously reported to describe no olfactory problems [1, 2]. A subsequent quantitative study found objectively reduced olfactory function in eight of nine patients tested (89%), with three patients (33%) aware of their olfactory impairment [3]. Variants can occur in the N-terminal glutamic acid-rich protein (GARP) domain or in the channel domain. The GARP domain is important in rod photoreceptors, but its role in olfactory neurons is less clear; an alternatively spliced variant (CNGB1b), lacking this domain, is expressed in olfactory neurons in rats [4]. We investigated awareness of olfactory problems in our molecularly characterised cohort, and explored in which domain variants occurred.

The electronic inherited retinal disease database of Moorfields Eye Hospital was searched for patients with a molecularly confirmed diagnosis of CNGB1-associated RP. Patients were asked (by telephone or during clinic visits) whether they were aware of problems with their sense of smell. Disease-causing variants were classified by occurrence within the GARP or channel domain of the protein. It was hypothesised that patients with both variants in the channel domain might be more likely to be aware of olfactory impairment (as a GARP domain change would not affect translation of a splice variant that lacked this domain).

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