18 Cadherin23 and protocadherin15 mutations have recently been shown to underlie USH1D (MIM 601067) and USH1F (MIM 602083), respectively. PDZ-domains are protein–protein interaction modules that allow the binding to and clustering of specific membrane-associated proteins, such as receptors and ion channels. 15 Mutations in the PDZ-domain-containing protein, harmonin, cause USH1C (MIM 276904) 16, 17. Mutations in the unconventional myosin MYO7A cause USH1B (MIM 276903 14) and in two unique cases also atypical USH phenotype similar to that of USH3. 12, 13 Four of the USH1 and the USH2A genes have been identified. While USH1 and USH2 map to at least 10 distinct loci, 3, 4, 5, 6, 7, 8, 9, 10, 11 only one locus for USH3 has been reported so far. 2 Progressive RP with variable age of onset occurs in all USH types. Postlingual progressive hearing loss and variable vestibular function characterise USH3 (MIM 276902). Three USH types are distinguished clinically. 1 Sensorineural hearing loss and retinitis pigmentosa (RP) characterise this group of autosomal recessive hereditary disorders. These account for more than half of the dual sensory deficit, with a prevalence of 1/10 000 in the age group of 30–50. 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.Ĭombined deafness and blindness in adults is most frequently caused by Usher syndromes (USH). The full length USH3A transcript encodes clarin-1, a four-transmembrane-domain protein, which defines a novel vertebrate-specific family of three paralogues. Expression of Ush3a transcripts was localised by whole mount in situ hybridisation to cochlear hair cells and spiral ganglion cells. 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. 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.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |