RGD Reference Report - Usher syndrome type I G (USH1G) is caused by mutations in the gene encoding SANS, a protein that associates with the USH1C protein, harmonin. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Usher syndrome type I G (USH1G) is caused by mutations in the gene encoding SANS, a protein that associates with the USH1C protein, harmonin.

Authors: Weil, D  El-Amraoui, A  Masmoudi, S  Mustapha, M  Kikkawa, Y  Laine, S  Delmaghani, S  Adato, A  Nadifi, S  Zina, ZB  Hamel, C  Gal, A  Ayadi, H  Yonekawa, H  Petit, C 
Citation: Weil D, etal., Hum Mol Genet. 2003 Mar 1;12(5):463-71.
RGD ID: 1599547
Pubmed: PMID:12588794   (View Abstract at PubMed)

Usher syndrome type I (USH1) is the most frequent cause of hereditary deaf-blindness in humans. Seven genetic loci (USH1A-G) have been implicated in this disease to date, and four of the corresponding genes have been identified: USH1B, C, D and F. We carried out fine mapping of USH1G (chromosome 17q24-25), restricting the location of this gene to an interval of 2.6 Mb and then screened genes present within this interval for mutations. The genes screened included the orthologue of the Sans gene, which is defective in the Jackson shaker deaf mutant and maps to the syntenic region in mice. In two consanguineous USH1G-affected families, we detected two different frameshift mutations in the SANS gene. Two brothers from a German family affected with USH1G were found to be compound heterozygotes for a frameshift and a missense mutation. These results demonstrate that SANS underlies USH1G. The SANS protein contains three ankyrin domains and a sterile alpha motif, and its C-terminal tripeptide presents a class I PDZ-binding motif. We showed, by means of co-transfection experiments, that SANS associates with harmonin, a PDZ domain-containing protein responsible for USH1C. In Jackson shaker mice the hair bundles, the mechanoreceptive structures of inner ear sensory cells, are disorganized. Based on the known interaction between USH1B (myosin VIIa), USH1C (harmonin) and USH1D (cadherin 23) proteins and the results obtained in this study, we suggest that a functional network formed by the USH1B, C, D and G proteins is responsible for the correct cohesion of the hair bundle.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
USH1GHumanDeafness  IAGP Usher syndrome more ...RGD 
Ush1gRatDeafness  ISOUSH1G (Homo sapiens)Usher syndrome more ...RGD 
Ush1gMouseDeafness  ISOUSH1G (Homo sapiens)Usher syndrome more ...RGD 


Genes (Rattus norvegicus)
Ush1g  (USH1 protein network component sans)

Genes (Mus musculus)
Ush1g  (USH1 protein network component sans)

Genes (Homo sapiens)
USH1G  (USH1 protein network component sans)