title: Alternative splice variants of the USH3A gene Clarin 1 (CLRN1).
abstract: Clarin 1 (CLRN1) is a four-transmembrane protein expressed in cochlear hair cells and neural retina, and when mutated it causes Usher syndrome type 3 (USH3). The main human splice variant of CLRN1 is composed of three exons that code for a 232-aa protein. In this study, we aimed to refine the structure of CLRN1 by an examination of transcript splice variants and promoter regions. Analysis of human retinal cDNA revealed 11 CLRN1 splice variants, of which 5 have not been previously reported. We studied the regulation of gene expression by several promoter domains using a luciferase assay, and identified 1000 nt upstream of the translation start site of the primary CLRN1 splice variant as the principal promoter region. Our results suggest that the CLRN1 gene is significantly more complex than previously described. The complexity of the CLRN1 gene and the identification of multiple splice variants may partially explain why mutations in CLRN1 result in substantial variation in clinical phenotype.
authors: The Folkhälsan Institute of Genetics, Biomedicum Helsinki, Helsinki, Finland. hanna.vastinsalo@helsinki.fi
authors: Hanna
authors: H
authors: Västinsalo
authors: Reetta
authors: R
authors: Jalkanen
authors: Astra
authors: A
authors: Dinculescu
authors: Juha
authors: J
authors: Isosomppi
authors: Scott
authors: S
authors: Geller
authors: John G
authors: JG
authors: Flannery
authors: William W
authors: WW
authors: Hauswirth
authors: Eeva-Marja
authors: EM
authors: Sankila
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D003051:Cochlea / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012160:Retina / Q000166:cytology / Q000378:metabolism; D052245:Usher Syndromes / Q000235:genetics / Q000503:physiopathology*
chemical_list: C437067:CLRN1 protein, human; D018076:DNA, Complementary; D008565:Membrane Proteins