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

被引:134
作者
Adato, A [1 ]
Vreugde, S
Joensuu, T
Avidan, N
Hamalainen, R
Belenkiy, O
Olender, T
Bonne-Tamir, B
Ben-Asher, E
Espinos, C
Millán, JM
Lehesjoki, AE
Flannery, JG
Avraham, KB
Pietrokovski, S
Sankila, EM
Beckmann, JS
Lancet, D
机构
[1] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel
[2] Weizmann Inst Sci, Crown Human Genome Ctr, IL-76100 Rehovot, Israel
[3] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel
[4] Univ Helsinki, Folkhalsan Inst Genet, Biomedicum Helsinki, Helsinki, Finland
[5] Univ Helsinki, Hosp Eye, Helsinki, Finland
[6] Univ Valencia, Dept Genet, E-46100 Burjassot, Spain
[7] Hosp La Fe, Genet Unit, E-46009 Valencia, Spain
[8] Univ Calif Berkeley, Sch Optometry, Berkeley, CA 94720 USA
[9] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA
关键词
USH3; deafness; retinitis pigmentosa; clarin; four-transmembrane-domain proteins;
D O I
10.1038/sj.ejhg.5200831
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:339 / 350
页数:12
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