Awareness of olfactory impairment in a cohort of patients with CNGB1-associated retinitis pigmentosa

CNGB1 ‐related rod‐cone dystrophy: A mutation review and update

“…This data is inferior to the previously reported prevalence of cystoid macular edema in RCD, which ranged among 26.9% and 58.6% (Adackapara et al, 2008; Hajali et al, 2008; Liew et al, 2019) but slightly higher than the 10% (1/10) reported in CNGB1 patients (Hull et al, 2017). As the shorter isoform CNGB1b transcribed from the CNGB1 locus is involved in the olfactory signal transduction, recent reports highlighted the presence of an impaired sense of smell in patients carrying biallelic CNGB1 variants, in particular in the channel domain (as the GARP domain is not expressed in the olfactory cells) (Afshar et al, 2019; Charbel Issa et al, 2018). Given the retrospective nature of our study, we did not have any data regarding the sense of smell in our cohort, neither subjective nor objective.…”

Mutational Spectrum, Ocular and Olfactory Phenotypes of CNGB1-Related RP-Olfactory Dysfunction Syndrome in a Multiethnic Cohort

“…In the French family, the previously described [ 13 ] c.2978G > T, p.Gly993Val variant (also a missense mutation) was observed in homozygosity, and all subjects presented normosmia in the odor identification test. We believe these missense variants may have a milder effect on olfactory function, even though they are both located in the channel domain and thus expected to cause olfactory dysfunction according to previous theories [ 6 , 13 , 15 ]. Since none of our families harbored variants in the GARP domain (not expressed in the OSNs), we could not assess the olfactory phenotype of mutations affecting this protein domain.…”

“…Despite being rare, the association between retinal degeneration and olfactory dysfunction has been reported in a few cases of Bardet-Biedl syndrome, Leber congenital amaurosis, and Refsum disease [ 30 ]. Recently, olfactory dysfunction in association with retinal degeneration has been described in CNGB1 -related disease and later coined RP-olfactory dysfunction syndrome [ 6 , 14 , 15 ]. In this multicenter, multiethnic study, we expand the mutational spectrum of CNGB1 -related disease by reporting two novel disease-causing variants.…”

“…The shorter transcript (CNGB1b protein) lacks the GARP domain and is expressed in OSNs [ 6 , 10 , 11 , 12 , 13 ]. Therefore, an abnormal CNG channel resulting from a mutation in CNGB1 affecting at least the channel transcript would be expected to result in a compromised retinal rod phototransduction and lack of conversion of odor stimuli into electric signals by the OSNs, leading to both retinal degeneration and olfactory dysfunction [ 6 , 13 , 14 , 15 ]—an association that was established in mice by Hüttl et al and Michalakis et al [ 16 , 17 ].…”

“…Even though CNGB1 -related retinal degeneration is well described, only three studies have associated CNGB1 variants with both RP and olfactory dysfunction [ 6 , 14 , 15 ]. The aim of this study was to report the molecular spectrum along with the ocular and olfactory phenotypes of a multiethnic cohort with genetically confirmed CNGB1 -associated retinal degeneration.…”