title: The first mutation in CNGA2 in two brothers with anosmia.
abstract: Isolated congenital anosmia (ICA) is a rare disorder, where otherwise healthy individuals present with an inability to smell since birth. A list of studies have described the genes involved in syndromic anosmia; however, the genetics of ICA is still in its infancy. Studies in mice show that the cyclic nucleotide-gated channel subunit CNGA2, expressed in the olfactory epithelium has a crucial role in olfactory signal transduction. We have identified a novel X-linked stop mutation in CNGA2 (c.634C>T, p.R212*) in two brothers with ICA using exome sequencing. No additional mutations in CNGA2 were identified in a cohort of 31 non-related ICA individuals. Magnetic resonance brain imaging revealed diminished olfactory bulbs and flattened olfactory sulci. This is the first report of a mutation in the cyclic nucleotide-gated gene CNGA2 and supports the critical role of this gene in human olfaction.
authors.affiliation: Willhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, The Faculty of Health Sciences, The University of Copenhagen, DK-2200, Copenhagen N, Denmark.
authors.forename: H G
authors.initials: HG
authors.lastname: Karstensen
authors.affiliation: Willhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, The Faculty of Health Sciences, The University of Copenhagen, DK-2200, Copenhagen N, Denmark.
authors.forename: Y
authors.initials: Y
authors.lastname: Mang
authors.affiliation: Interdisciplinary Center for Smell & Taste, Department of Otorhinolaryngology, Technical University of Dresden Medical School, 01307, Dresden, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Fark
authors.affiliation: Interdisciplinary Center for Smell & Taste, Department of Otorhinolaryngology, Technical University of Dresden Medical School, 01307, Dresden, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Hummel
authors.affiliation: Willhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, The Faculty of Health Sciences, The University of Copenhagen, DK-2200, Copenhagen N, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Tommerup
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D000857:Olfaction Disorders / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D009830:Olfactory Bulb / Q000473:pathology; D010375:Pedigree; D016415:Sequence Alignment; D035781:Siblings
chemical_list: C518241:CNGA2 protein, human; D054815:Cyclic Nucleotide-Gated Cation Channels
keywords: cyclic nucleotide-gated channel alpha 2; first mutation; isolated congenital general anosmia; olfaction