MYO7A and USH2A gene sequence variants in Italian patients with Usher syndrome.

PURPOSE: 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.

Testing the visual field of children and adults with Rarebit: The role of task repetition on sensitivity.

Rarebit is a simple and user-friendly perimetry that tests the visual field by using tiny supra-threshold dot stimuli. It appears to be especially useful for examining the visual field of children who are under 12 years of age. However, previous data showed that the number of errors was higher in children than adults. We ask whether the different number of errors in these two groups depended on task learning and whether it may be accounted for by sensitivity differences or a response bias. Thirty-one children between 9 and 12 years of age and thirty-nine adults were tested three times with Rarebit perimetry. A bias-free sensitivity index, d', rather than the simple hit rate, revealed a group difference that remained after extensive task repetition. Indeed, d' increased with task learning in a similar way in the two groups so that group difference remained after practice. The response bias differed in the two groups, being conservative in the older group (criterion C >0) and liberal in the younger (criterion C < 0). Both biases disappeared with task learning in the third session, suggesting that response bias cannot account for the group difference in sensitivity after practice. When bias-free measures of sensitivity are used and task learning effects are minimized, Rarebit perimetry may be a more valuable method than simple mean hit rate (MHR) to enlighten sensitivity differences in the visual field assessment within the pediatric population.