Novel mutations in the USH1C gene in Usher syndrome patients.

Abstract

PURPOSE:

Usher syndrome type I (USH1) is an autosomal recessive disorder characterized by severe-profound sensorineural hearing loss, retinitis pigmentosa, and vestibular areflexia. To date, five USH1 genes have been identified. One of these genes is Usher syndrome 1C (USH1C), which encodes a protein, harmonin, containing PDZ domains. The aim of the present work was the mutation screening of the USH1C gene in a cohort of 33 Usher syndrome patients, to identify the genetic cause of the disease and to determine the relative involvement of this gene in USH1 pathogenesis in the Spanish population.

METHODS:

Thirty-three patients were screened for mutations in the USH1C gene by direct sequencing. Some had already been screened for mutations in the other known USH1 genes (myosin VIIA [MYO7A], cadherin-related 23 [CDH23], protocadherin-related 15 [PCDH15], and Usher syndrome 1G [USH1G]), but no mutation was found.

RESULTS:

Two novel mutations were found in the USH1C gene: a non-sense mutation (p.C224X) and a frame-shift mutation (p.D124TfsX7). These mutations were found in a homozygous state in two unrelated USH1 patients.

CONCLUSIONS:

In the present study, we detected two novel pathogenic mutations in the USH1C gene. Our results suggest that mutations in USH1C are responsible for 1.5% of USH1 disease in patients of Spanish origin (considering the total cohort of 65 Spanish USH1 patients since 2005), indicating that USH1C is a rare form of USH in this population.

• Authors: María José Aparisi, Gema García-García, Teresa Jaijo, Regina Rodrigo, Claudio Graziano, Marco Seri, Tulay Simsek, Enver Simsek, Sara Bernal, Montserrat Baiget, Herminio Pérez-Garrigues, Elena Aller, José María Millán
• Journal: Molecular vision (Mol Vis) Vol. 16 Pg. 2948-54 (Dec 31 2010) ISSN: 1090-0535 [Electronic] United States
• PMID: 21203349 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Cell Cycle Proteins
• Cytoskeletal Proteins
• MYO7A protein, human
• Myosin VIIa
• USH1C protein, human
• Myosins

Topics

• Adaptor Proteins, Signal Transducing (genetics)
• Base Sequence
• Cell Cycle Proteins
• Chromosome Segregation (genetics)
• Cohort Studies
• Cytoskeletal Proteins
• DNA Mutational Analysis
• Family
• Female
• Genetic Linkage
• Genetic Loci (genetics)
• Humans
• Male
• Molecular Sequence Data
• Mutation (genetics)
• Myosin VIIa
• Myosins (genetics)
• Pedigree
• Usher Syndromes (genetics)