June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Targeted next generation sequencing in Italian patients with Usher syndrome: phenotype genotype correlations
Author Affiliations & Notes
  • Chiara M Eandi
    Department of Surgical Sciences, Eye Clinic, University Torino, Torino, Italy
  • Alessandro Mariottini
    Diagnostic Genetic Unit AOU Careggi , Firenze, Italy
  • Camilla Alovisi
    Department of Surgical Sciences, Eye Clinic, University Torino, Torino, Italy
  • Francesca Torricelli
    Diagnostic Genetic Unit AOU Careggi , Firenze, Italy
  • Luca Musso
    Department of Surgical Sciences, Eye Clinic, University Torino, Torino, Italy
  • Cristiana Marchese
    Inherited retinal dystrophies Unit, Azienda Ospedaliera Ordine Mauriziano Torino, Torino, Italy
  • Footnotes
    Commercial Relationships   Chiara Eandi, None; Alessandro Mariottini, None; Camilla Alovisi, None; Francesca Torricelli, None; Luca Musso, None; Cristiana Marchese, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2768. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : 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).

Methods : 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.

Results : 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

Conclusions : 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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