Olfactory Dysfunction in Patients With CNGB1-Associated Retinitis Pigmentosa

TY - JOUR

T1 - Olfactory Dysfunction in Patients With CNGB1-Associated Retinitis Pigmentosa

AU - Charbel Issa, Peter

AU - Reuter, Peggy

AU - Kühlewein, Laura

AU - Birtel, Johannes

AU - Gliem, Martin

AU - Tropitzsch, Anke

AU - Whitcroft, Katherine L

AU - Bolz, Hanno J

AU - Ishihara, Kenji

AU - MacLaren, Robert E

AU - Downes, Susan M

AU - Oishi, Akio

AU - Zrenner, Eberhart

AU - Kohl, Susanne

AU - Hummel, Thomas

PY - 2018/7/1

Y1 - 2018/7/1

N2 - 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 series was 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.

AB - 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 series was 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.

KW - Adult

KW - Aged

KW - Cyclic Nucleotide-Gated Cation Channels/genetics

KW - DNA Mutational Analysis

KW - Electroencephalography

KW - Electroretinography

KW - Female

KW - High-Throughput Nucleotide Sequencing

KW - Humans

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Mutation

KW - Olfaction Disorders/diagnosis

KW - Olfactory Perception

KW - Ophthalmoscopy

KW - Phenotype

KW - Retinitis Pigmentosa/diagnosis

KW - Tomography, Optical Coherence

U2 - 10.1001/jamaophthalmol.2018.1621

DO - 10.1001/jamaophthalmol.2018.1621

M3 - SCORING: Journal article

C2 - 29800053

VL - 136

SP - 761

EP - 769

JO - JAMA OPHTHALMOL

JF - JAMA OPHTHALMOL

SN - 2168-6165

IS - 7

ER -