title: USH3A transcripts encode clarin-1, a four-transmembrane-domain protein with a possible role in sensory synapses.
abstract: Usher syndrome type 3 (USH3) is an autosomal recessive disorder characterised by the association of post-lingual progressive hearing loss, progressive visual loss due to retinitis pigmentosa and variable presence of vestibular dysfunction. Because the previously defined transcripts do not account for all USH3 cases, we performed further analysis and revealed the presence of additional exons embedded in longer human and mouse USH3A transcripts and three novel USH3A mutations. Expression of Ush3a transcripts was localised by whole mount in situ hybridisation to cochlear hair cells and spiral ganglion cells. The full length USH3A transcript encodes clarin-1, a four-transmembrane-domain protein, which defines a novel vertebrate-specific family of three paralogues. Limited sequence homology to stargazin, a cerebellar synapse four-transmembrane-domain protein, suggests a role for clarin-1 in hair cell and photoreceptor cell synapses, as well as a common pathophysiological pathway for different Usher syndromes.
authors.affiliation: Department of Molecular Genetics and The Crown Human Genome Center, The Weizmann Institute of Science, Rehovot, 76100, Israel. Ivadato@bioinfo.weizmann.ac.il
authors.forename: Avital
authors.initials: A
authors.lastname: Adato
authors.forename: Sarah
authors.initials: S
authors.lastname: Vreugde
authors.forename: Tarja
authors.initials: T
authors.lastname: Joensuu
authors.forename: Nili
authors.initials: N
authors.lastname: Avidan
authors.forename: Riikka
authors.initials: R
authors.lastname: Hamalainen
authors.forename: Olga
authors.initials: O
authors.lastname: Belenkiy
authors.forename: Tsviya
authors.initials: T
authors.lastname: Olender
authors.forename: Batsheva
authors.initials: B
authors.lastname: Bonne-Tamir
authors.forename: Edna
authors.initials: E
authors.lastname: Ben-Asher
authors.forename: Carmen
authors.initials: C
authors.lastname: Espinos
authors.forename: José M
authors.initials: JM
authors.lastname: Millán
authors.forename: Anna-Elina
authors.initials: AE
authors.lastname: Lehesjoki
authors.forename: John G
authors.initials: JG
authors.lastname: Flannery
authors.forename: Karen B
authors.initials: KB
authors.lastname: Avraham
authors.forename: Shmuel
authors.initials: S
authors.lastname: Pietrokovski
authors.forename: Eeva-Marja
authors.initials: EM
authors.lastname: Sankila
authors.forename: Jacques S
authors.initials: JS
authors.lastname: Beckmann
authors.forename: Doron
authors.initials: D
authors.lastname: Lancet
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000235:genetics; D002874:Chromosome Mapping; D005260:Female; D020869:Gene Expression Profiling; D006198:Hair Cells, Auditory / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010802:Phylogeny; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D020539:Sequence Analysis, Protein; D013569:Synapses / Q000502:physiology*
chemical_list: C491912:CACNG2 protein, human; C437067:CLRN1 protein, human; C113940:Cacng2 protein, mouse; D015220:Calcium Channels; C512668:Clrn1 protein, mouse; D008565:Membrane Proteins