Two novel disease-causing mutations in the CLRN1 gene in patients with Usher syndrome type 3.

Molecular Vision

PubMedID: 23304067

García-García G, Aparisi MJ, Rodrigo R, Sequedo MD, Espinós C, Rosell J, Olea JL, Mendívil MP, Ramos-Arroyo MA, Ayuso C, Jaijo T, Aller E, Millán JM. Two novel disease-causing mutations in the CLRN1 gene in patients with Usher syndrome type 3. Mol Vis. 2013;183070-8.
PURPOSE
To identify the genetic defect in Spanish families with Usher syndrome (USH) and probable involvement of the CLRN1 gene.

METHODS
DNA samples of the affected members of our cohort of USH families were tested using an USH genotyping array, and/or genotyped with polymorphic markers specific for the USH3A locus. Based on these previous analyses and clinical findings, CLRN1 was directly sequenced in 17 patients susceptible to carrying mutations in this gene.

RESULTS
Microarray analysis revealed the previously reported mutation p.Y63X in two unrelated patients, one of them homozygous for the mutation. After CLRN1 sequencing, we found two novel mutations, p.R207X and p.I168N. Both novel mutations segregated with the phenotype.

CONCLUSIONS
To date, 18 mutations in CLRN1 have been reported. In this work, we report two novel mutations and a third one previously identified in the Spanish USH sample. The prevalence of CLRN1 among our patients with USH is low.