title: MYO7A and USH2A gene sequence variants in Italian patients with Usher syndrome.
abstract: OBJECTIVE
  To analyze the spectrum of sequence variants in the MYO7A and USH2A genes in a group of Italian patients affected by Usher syndrome (USH).
  
  
  METHODS
  Thirty-six Italian patients with a diagnosis of USH were recruited. They received a standard ophthalmologic examination, visual field testing, optical coherence tomography (OCT) scan, and electrophysiological tests. Fluorescein angiography and fundus autofluorescence imaging were performed in selected cases. All the patients underwent an audiologic examination for the 0.25-8,000 Hz frequencies. Vestibular function was evaluated with specific tests. DNA samples were analyzed for sequence variants of the MYO7A gene (for USH1) and the USH2A gene (for USH2) with direct sequencing techniques. A few patients were analyzed for both genes.
  
  
  RESULTS
  In the MYO7A gene, ten missense variants were found; three patients were compound heterozygous, and two were homozygous. Thirty-four USH2A gene variants were detected, including eight missense variants, nine nonsense variants, six splicing variants, and 11 duplications/deletions; 19 patients were compound heterozygous, and three were homozygous. Four MYO7A and 17 USH2A variants have already been described in the literature. Among the novel mutations there are four USH2A large deletions, detected with multiplex ligation dependent probe amplification (MLPA) technology. Two potentially pathogenic variants were found in 27 patients (75%). Affected patients showed variable clinical pictures without a clear genotype-phenotype correlation.
  
  
  CONCLUSIONS
  Ten variants in the MYO7A gene and 34 variants in the USH2A gene were detected in Italian patients with USH at a high detection rate. A selective analysis of these genes may be valuable for molecular analysis, combining diagnostic efficiency with little time wastage and less resource consumption.
authors.affiliation: Department of Ophthalmology, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sodi
authors.affiliation: Department of Genetic Diagnosis, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mariottini
authors.affiliation: Department of Genetic Diagnosis, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Passerini
authors.affiliation: Department of Ophthalmology, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Murro
authors.affiliation: Department of Ophthalmology, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors.forename: Iryna
authors.initials: I
authors.lastname: Tachyla
authors.affiliation: Department of Otolaryngology, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bianchi
authors.affiliation: Department of Ophthalmology, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Menchini
authors.affiliation: Department of Genetic Diagnosis, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Torricelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D052245:Usher Syndromes / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult
chemical_list: D016326:Extracellular Matrix Proteins; C000631455:MYO7A protein, human; D000081412:Myosin VIIa; C112735:USH2A protein, human; D009218:Myosins