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Chiara M Eandi, Alessandro Mariottini, Camilla Alovisi, Francesca Torricelli, Luca Musso, Cristiana Marchese; Targeted next generation sequencing in Italian patients with Usher syndrome: phenotype genotype correlations. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2768.
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This study analysed the genotype-phenotype correlation in Usher syndrome (USH) patients with known and novel mutations in Usher related genes identified with targeted next generation sequencing (NGS).
This is a retrospective study. A group of 19 consecutive Italian patients (14 males and 5 females) from 15 unrelated families with a clinical diagnosis of USH underwent to a complete ophthalmic examination, electroretinogram (ERG), visual evoked potentials (VEP), visual field test, and optic coherence tomography (OCT). Targeted next generation sequencing (NGS) of coding regions and exon-intron junctions of a panel of 11 Usher related genes (MYO7A, CDH23, PCDH15, USH1C, USH1G, USH2A, ADGVR1/GPR98, DFNB31, CLRN1, PDZD7, and HARS) was performed.
NGS of 11 Usher related genes (MYO7A, CDH23, PCDH15, USH1C, USH1G, USH2A, ADGVR1/GPR98, DFNB31, CLRN1, PDZD7, HARS) was applied to 19 clinical diagnosed USH patients (4 type 1, 15 type 2). Retrospective analysis of phenotypic characteristics was conducted, particularly, age of onset of deafness, visual deficiency and equilibrium impairment.35 pathogenic variants - 22 previously reported and 13 novel - were identified in four genes (USH2A, MYO7A, ADGRV1/GPR98, CDH23). Biallelic MYO7A and USH2A mutations were detected in all USH1 and USH2 patients, respectively. In two patients one of the USH2A alleles carried two mutations. In USH1 deafness occurred in early childhood (5 months) and visual impairment at 1, 4 and 6 years with the exception of one patient (20 years). In patients with USH2 deafness onset ranged from 11 months to 14 years. A homozygous deletion/duplication in USH2A was detected in the patient with early deafness onset. Visual impairment onset was from 10 to 30 years. A homozygous large deletion (exon 23 to 32) was associated with early symptoms
The type of mutation in USH2A and MYO7A genes affects the age of onset of deafness and visual impairment. The definition of the genotype by segregation analysis is indicated due to the presence of alleles with more than one mutation. Genotype knowledge may assist in both clinical diagnosis and genetic counselling of these patients.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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