title: Molecular epidemiology of Usher syndrome in Italy.
abstract: OBJECTIVE
  Usher syndrome is an autosomal recessive disorder characterized by hearing and vision loss. Usher syndrome is divided into three clinical subclasses (type 1, type 2, and type 3), which differ in terms of the severity and progression of hearing loss and the presence or absence of vestibular symptoms. Usher syndrome is defined by significant genetic heterogeneity, with at least 12 distinct loci described and 9 genes identified. This study aims to provide a molecular epidemiology report of Usher syndrome in Italy.
  
  
  METHODS
  Molecular data have been obtained on 75 unrelated Italian patients using the most up-to date technology available for the screening of Usher syndrome gene mutations, i.e., the genotyping microarray developed by Asper Biotech (Tartu, Estonia), which simultaneously investigates 612 different marker positions using the well established arrayed primer extension methodology (APEX).
  
  
  RESULTS
  Using this method, we found that 12% of cases (9 out of 75) harbored homozygous or compound heterozygous mutations in the gene positions analyzed, whereas 20% (15 out of 75) of the patients were characterized by the presence of only one mutated allele based on the positions analyzed. One patient was found to be compound heterozygous for mutations in two different genes and this represents an example of possible digenic inheritance in Usher syndrome. A total of 66.6% of cases (50 out of 75) were found to be completely negative for the presence of Usher syndrome gene mutations in the detected positions. Mutations detected by the array were confirmed by direct sequencing.
  
  
  CONCLUSIONS
  These findings highlight the efficacy of the APEX-based genotyping approach in the molecular assessment of Usher patients, suggesting the presence of alleles not yet identified and/or the involvement of additional putative genes that may account for the pathogenesis of Usher syndrome.
authors: Medical Genetics, Department of Reproductive Sciences, Development and Public Health, IRCCS-Burlo Garofolo Children Hospital, University of Trieste, Trieste, 34100 Italy.
authors: Diego
authors: D
authors: Vozzi
authors: Anu
authors: A
authors: Aaspõllu
authors: Emmanouil
authors: E
authors: Athanasakis
authors: Anna
authors: A
authors: Berto
authors: Antonella
authors: A
authors: Fabretto
authors: Danilo
authors: D
authors: Licastro
authors: Maigi
authors: M
authors: Külm
authors: Francesco
authors: F
authors: Testa
authors: Patrizia
authors: P
authors: Trevisi
authors: Marju
authors: M
authors: Vahter
authors: Carmela
authors: C
authors: Ziviello
authors: Alessandro
authors: A
authors: Martini
authors: Francesca
authors: F
authors: Simonelli
authors: Sandro
authors: S
authors: Banfi
authors: Paolo
authors: P
authors: Gasparini
mesh_terms: D017668:Age of Onset; D000483:Alleles; D004252:DNA Mutational Analysis; D018740:Genetic Heterogeneity; D005838:Genotype; D034381:Hearing Loss / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007558:Italy; D017720:Molecular Epidemiology / Q000379:methods*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012720:Severity of Illness Index; D052245:Usher Syndromes / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology