Olfactory dysfunction in patients with CNGB1-associated retinitis pigmentosa

Abstract

IMPORTANCE Co-occurrence of retinitis pigmentosa (RP) and olfactory dysfunction may have a common genetic cause. OBJECTIVE To report olfactory function and the retinal phenotype in patients with biallelic mutations in CNGB1, a gene coding for a signal transduction channel subunit expressed in rod photoreceptors and olfactory sensory neurons. DESIGN, SETTING, AND PARTICIPANTS This case serieswas conducted from August 2015 through July 2017. The setting was a multicenter study involving 4 tertiary referral centers for inherited retinal dystrophies. Participants were 9 patients with CNGB1-associated RP. MAIN OUTCOMES AND MEASURES Results of olfactory testing, ocular phenotyping, and molecular genetic testing using targeted next-generation sequencing. RESULTS Nine patients were included in the study, 3 of whom were female. Their ages ranged between 34 and 79 years. All patients had an early onset of night blindness but were usually not diagnosed as having RP before the fourth decade because of slow retinal degeneration. Retinal features were characteristic of a rod-cone dystrophy. Olfactory testing revealed reduced or absent olfactory function, with all except one patient scoring in the lowest quartile in relation to age-related norms. Brain magnetic resonance imaging and electroencephalography measurements in response to olfactory stimulation were available for 1 patient and revealed no visible olfactory bulbs and reduced responses to odor, respectively. Molecular genetic testing identified 5 novel (c.1312C>T, c.2210G>A, c.2492+1G>A, c.2763C>G, and c.3044-3050delGGAAATC) and 5 previously reported mutations in CNGB1. CONCLUSIONS AND RELEVANCE Mutations in CNGB1 may cause an autosomal recessive RP-olfactory dysfunction syndrome characterized by a slow progression of retinal degeneration and variable anosmia or hyposmia.