6533b871fe1ef96bd12d242b
RESEARCH PRODUCT
Microarray-based mutation analysis of 183 Spanish families with Usher syndrome.
C. NájeraGema García-garcíaManuel Díaz-llopisTeresa JaijoMaría José AparisiMontserrat BaigetGuillermo AntiñoloElena AllerCarmen AyusoMagdalena BeneytoAlmudena Avila-fernandezIsabel BarraganMaigi KülmJosé M. MillánSara Bernalsubject
medicine.medical_specialtyGenotypeMicroarrayUsher syndromeDNA Mutational AnalysisCadherin Related ProteinsCell Cycle ProteinsNerve Tissue ProteinsMyosinsBiologymedicine.disease_causePolymerase Chain ReactionReceptors G-Protein-CoupledMolecular geneticsGenotypemedicineotorhinolaryngologic diseasesHumansGenotypingAllelesAdaptor Proteins Signal TransducingOligonucleotide Array Sequence AnalysisGeneticsExtracellular Matrix ProteinsMutationGene Expression ProfilingHaplotypeMembrane ProteinsCadherinsmedicine.diseaseGene expression profilingCytoskeletal ProteinsSpainMyosin VIIaMutationUsher Syndromesdescription
PURPOSE. The purpose of this study was to test the ability of the genotyping microarray for Usher syndrome (USH) to identify the mutations responsible for the disease in a cohort of 183 patients with USH. METHODS. DNA from 183 patients with Usher syndrome from the Spanish population was analyzed using a genotyping microarray containing 429 previously identified disease-associated variants in eight USH genes. Mutations detected by the array were confirmed by direct sequencing. Haplotype analysis was also performed in families carrying common Spanish mutations. RESULTS. The genotyping microarray identified 43 different variants, divided into 32 disease causative and 11 probably non-pathologic. Mutations were detected in 62 patients with USH (33.9%). According to the clinical classification of patients, pathologic variants were detected in 31.4% patients with USH1, 39.4% of with USH2, 22.2% with USH3 and 15.8% with unclassified Usher syndrome. Ninety-seven pathologic alleles were detected, corresponding to 26.5% of expected alleles. The USH2A mutations p. C3267R and p. T3571M were revealed as common in the Spanish population, and two major haplotypes linked to these mutations were observed. CONCLUSIONS. The genotyping microarray is a robust, low-cost, rapid technique that is effective for the genetic study of patients with USH. However, it also indicates variants of unclear pathologic nature and detection failures have also been observed. Results must be confirmed by direct sequencing to avoid misdiagnosis, and continuous updates of the microarray should be performed to increase the efficiency and rate of detection of mutations. (Invest Ophthalmol Vis Sci. 2010;51:1311-1317) DOI:10.1167/iovs.09-4085
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-01-01 |