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

Abstract

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The Natural History of CNGB1-Related Retinopathy: A Longitudinal Phenotypic Analysis

“…Abnormal hyperAF ring phenotypes on FAF have been reported in 59–68% of RP patients, depending on genetic cause [ 31 , 32 ]. A recent review identified ring phenotypes on quantitative FAF in 79.3% of RP patients with CNGB1 mutations, similar to our cohort of 69.7% [ 11 ]. These differing FAF phenotypes did not appear correlated with age or genotype in this study.…”

“…There was no clear inflection point to determine if the rate changed with age. ERM prevalence in our study is higher than in previously reported CNGB1 cohorts (34.8% in Nassisi et al and 20% in Hull et al), but has been reported in up to 64% from other RP cohorts, precluding the use of central retinal thickness as a reliable outcome measure [ 10 , 11 , 30 ]. Abnormal hyperAF ring phenotypes on FAF have been reported in 59–68% of RP patients, depending on genetic cause [ 31 , 32 ].…”

“…There are 84 known disease-causing CNGB1 variants including 24 missense variants, 21 nonsense, 19 splicing defects, 10 small deletions, 1 small insertion, 1 small insertion–deletion, 7 small duplications, and 1 gross deletion, and this is comprehensively discussed in a recent review [ 11 ]. The known variants span the entire gene with no known cluster regions.…”

“…The known variants span the entire gene with no known cluster regions. No genotype-phenotype correlations have been identified to date, however there are only limited reports describing CNGB1-RP phenotypes [ 5 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Animal modelling of CNGB1-related RP has successfully recapitulated the human disease.…”

“…Constriction of hyperAF rings have correlated with disease progression in other RP subtypes [ 22 , 28 ], and have shown to have detectable changes in area over a 2–5 year period in a small CNGB1-related RP cohort of three patients [ 12 ]. Central retinal thickness is not a suitable metric due to confounding factors including epiretinal membrane (ERM) and cystoid macular oedema (CMO), prevalent in these patients [ 11 ]. This is in line with a previous FDA assessment of age-related macular degeneration (AMD), whereby considerable variability has been previously shown in metrics such as visual acuity, retinal thickness, and visual fields, whereas EZ length and hyperAF ring area may be more useful in measuring photoreceptor degeneration [ 29 ].…”