USH3A transcripts encode clarin-1, a four-transmembrane-domain protein with a possible role in sensory synapses

Avital Adato, Sarah Vreugde, Tarja Joensuu, Nili Avidan, Riikka Hamalainen, Olga Belenkiy, Tsviya Olender, Batsheva Bonne-Tamir, Edna Ben-Asher, Carmen Espinos, José M. Millán, Anna Elina Lehesjoki, John G. Flannery, Karen B. Avraham, Shmuel Pietrokovski, Eeva Marja Sankila, Jacques S. Beckmann, Doron Lancet

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

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.

Original languageEnglish
Pages (from-to)339-350
Number of pages12
JournalEuropean Journal of Human Genetics
Volume10
Issue number6
DOIs
StatePublished - 2002

Funding

FundersFunder number
Finnish Eye and Tissue Bank Foundation
Israeli Ministry of Science Culture and Sports
Oskar Oflund FoundationTYH9235
Maud Kuistilan Muistosäätiö
Foundation Fighting Blindness
European CommissionQLG2-CT-1999-00988
Weizmann Institute of Science
Alfried Krupp von Bohlen und Halbach-Stiftung
Silmäsäätiö
Crown Human Genome Center

    Keywords

    • Clarin
    • Deafness
    • Four-transmembrane-domain proteins
    • Retinitis pigmentosa
    • USH3

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