The first mutation in <i><scp>CNGA2</scp></i> in two brothers with anosmia

Karstensen, Helena Gásdal; Mang, Yuan; Fark, Therese; Hummel, Thomas; Tommerup, Niels

doi:10.1111/cge.12491

Cited by 32 publications

(45 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We identified a novel stop-gain mutation in CNGA2 gene that in concert with Cnga2 knockout mice and results of the Karstensen et al . study 3 further supports the role of CNGA2 in the pathogenesis of ICA in humans.…”

Section: Introductionsupporting

confidence: 72%

“…Rarely, however, it can occur as a congenital condition (prevalence 1 in 10,000) 21 (Isolated Congenital Anosmia) (Online Mendelian Inheritance in Man [OMIM] % 107200). Few candidate genes have been identified as potential causal genes for ICA in humans 3, 6, 11–13, 22 . For instance, Karstensen et al .…”

Section: Discussionmentioning

confidence: 99%

“…For instance, Karstensen et al . 3 reported a mutation in CNGA2 in two brothers with an X-linked pattern of ICA 3 . However, the lack of additional family members precluded definitive assignment of this gene as associated with this disease.…”

Section: Discussionmentioning

confidence: 99%

“…first reported ICA as a potentially hereditary trait nearly 100 years ago 10 , there have been few candidate genes identified as the potential genetic cause for ICA 3, 6, 11–13 . Moreover, most reported anosmia cases are inherited through autosomal dominant patterns 2, 14 , however, in some instances, it is an X-linked trait 3, 6, 10 . For instance, In 2015, Karstensen et al .…”

Section: Introductionmentioning

confidence: 99%

“…For instance, In 2015, Karstensen et al . for the first time reported a hemizygous nonsense mutation in CNGA2 in an ICA family (two brothers) with an X-linked pattern of inheritance 3 , but the lack of additional family members precluded definitive assignment of this gene as associated with this disease. CNGA2 encodes the alpha subunit of a cyclic nucleotide-gated olfactory channel.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Isolated Congenital Anosmia and CNGA2 Mutation

Sailani

Inlora

MirMazlomi³

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Isolated congenital anosmia (ICA) is a rare condition that is associated with life-long inability to smell. Here we report a genetic characterization of a large Iranian family segregating ICA. Whole exome sequencing in five affected family members and five healthy members revealed a stop gain mutation in CNGA2 (OMIM 300338) (chrX:150,911,102; CNGA2. c.577C > T; p.Arg193*). The mutation segregates in an X-linked pattern, as all the affected family members are hemizygotes, whereas healthy family members are either heterozygote or homozygote for the reference allele. cnga2 knockout mice are congenitally anosmic and have abnormal olfactory system physiology, additionally Karstensen et al. recently reported two anosmic brothers sharing a CNGA2 truncating variant. Our study in concert with these findings provides strong support for role of CNGA2 gene with pathogenicity of ICA in humans. Together, these results indicate that mutations in key olfactory signaling pathway genes are responsible for human disease.

show abstract

Section: Introductionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Isolated Congenital Anosmia and CNGA2 Mutation

Sailani

Inlora

MirMazlomi³

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

Olfactory Dysfunction in Patients WithCNGB1-Associated Retinitis Pigmentosa

et al. 2018

View full text Add to dashboard Cite

etinitis pigmentosa (RP) (OMIM 26800) is a genetically heterogeneous disease characterized by poor night vision and loss of peripheral visual field owing to a decline in rod-dependent vision. Later in the disease course, cones and thus the central visual field and visual acuity may also be affected. Retinitis pigmentosa is caused by mutations in genes coding for proteins involved in photoreceptor function, structure, and/or maintenance. When the gene product is expressed exclusively in the retina or when its lack is compensated for in other tissues, the disease remains restricted to the retina. However, significant expression of the gene product in other organs may result in syndromic RP with morphological and/or functional consequences affecting other organs. Cyclic nucleotide-gated (CNG) channels are key components for signal transduction in photoreceptors and olfactory sensory neurons (OSNs). 1 They function as tetramers composed of α and β subunits. Specific types of heterotetramers are expressed in different sensory cells. For example, the rod CNG channel consists of 3 CNGA1 subunits and 1 CNGB1 subunit, 2 the cone CNG channel consists of 3 CNGA3 subunits and 1 CNGB3 subunit, 3,4 and the CNG channel of OSNs (olfCNG) consists of 2 CNGA2 subunits, 1 CNGA4 subunit, and 1 CNGB1b subunit. 5 Therefore, only the CNGB1 subunit is involved in both photoreceptor and olfactory signal transduction. In contrast to most CNGA subunits that are regarded as main subunits 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_3050...

show abstract

Olfaction

Mainland

2018

Stevens' Handbook of Experimental Psychology and Cognitive Neuroscience

View full text Add to dashboard Cite

To detect and organize trillions of possible volatile molecules, the human olfactory system deploys approximately 3% of the genes in the human genome as olfactory receptors. Our understanding of how the olfactory system organizes the resulting information has many gaps, and relative to other sensory systems, our current ability to measure and reproduce smells is poor. Here we cover the anatomy, circuitry, and psychophysics of olfaction, with an emphasis on the gaps that prevent us from measuring an odor, representing it digitally, and reproducing a perceptual target from a set of sensory primaries.

show abstract

The first mutation in CNGA2 in two brothers with anosmia

Cited by 32 publications

References 34 publications

Isolated Congenital Anosmia and CNGA2 Mutation

Isolated Congenital Anosmia and CNGA2 Mutation

Olfactory Dysfunction in Patients WithCNGB1-Associated Retinitis Pigmentosa

Olfaction

Contact Info

Product

Resources

About