USH3A transcripts encode clarin-1, a four-transmembrane-domain protein with a possible role in sensory synapses.
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.
Adato
Avital
A
Department of Molecular Genetics and The Crown Human Genome Center, The Weizmann Institute of Science, Rehovot, 76100, Israel. Ivadato@bioinfo.weizmann.ac.il
Vreugde
Sarah
S
Joensuu
Tarja
T
Avidan
Nili
N
Hamalainen
Riikka
R
Belenkiy
Olga
O
Olender
Tsviya
T
Bonne-Tamir
Batsheva
B
Ben-Asher
Edna
E
Espinos
Carmen
C
Millán
José M
JM
Lehesjoki
Anna-Elina
AE
Flannery
John G
JG
Avraham
Karen B
KB
Pietrokovski
Shmuel
S
Sankila
Eeva-Marja
EM
Beckmann
Jacques S
JS
Lancet
Doron
D
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*
C491912:CACNG2 protein, human; C437067:CLRN1 protein, human; C113940:Cacng2 protein, mouse; D015220:Calcium Channels; C512668:Clrn1 protein, mouse; D008565:Membrane Proteins