September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Diagnostic Utility of a Next Generation Sequencing Retinal Panel in a Māori and Polynesian population with Inherited Retinal Disease
Author Affiliations & Notes
  • Andrea L Vincent
    Ophthalmology, New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand
    Eye Department, Greenlane Clinical Centre, Auckland District Health Board, Auckland, New Zealand
  • Alix Coysh
    Ophthalmology, New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand
  • Katherine Van Bysterveldt
    Ophthalmology, New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand
  • Verity Frances Oliver
    Ophthalmology, New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand
  • Graeme C.M. Black
    Manchester Centre for Genomic Medicine, Institute of Human Development,, University of Manchester, Manchester, United Kingdom
  • Footnotes
    Commercial Relationships   Andrea Vincent, None; Alix Coysh, None; Katherine Van Bysterveldt, None; Verity Oliver, None; Graeme Black, None
  • Footnotes
    Support  Save SIght Society NZ, Retina New Zealand, Fight for Sight UK, Ombler Trust, University of Auckland
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3157. doi:
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      Andrea L Vincent, Alix Coysh, Katherine Van Bysterveldt, Verity Frances Oliver, Graeme C.M. Black; Diagnostic Utility of a Next Generation Sequencing Retinal Panel in a Māori and Polynesian population with Inherited Retinal Disease. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3157.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Small ethnically diverse populations represent a diagnostic challenge for genetic characterisation of inherited retinal disease (IRD), because of the presence of rare founder mutations, and an underrepresentation in databases of human variation. We aim to elucidate the genetic cause in Māori and Polynesian patients with IRD, using a next-generation sequencing (NGS) targeted retinal disease gene panel, and to establish phenotype-genotype correlations.

Methods : Patients of Māori and Polynesian ancestry, genetically uncharacterised with microarrays (Asper), were identified from the Inherited Retinal Disease Database. Clinical history, examination, and imaging were obtained for each patient. DNA underwent NGS of a targeted retinal disease gene panel (Manchester, UK). An ethnically matched control population was screened for identified changes.

Results : In the cohort of 28 patients (recessive rod cone dystrophy (ARRP n=15), dominant RP (ADRP n=2), Leber congenital amaurosis (LCA n=3), Maculopathy ( n=4) or Cone/ Cone-rod dystrophy (CORD n=4), 21 unique, pathogenic variants (12 novel) were observed, allowing a definitive genetic diagnosis in 16/28 (57%). Homozygosity was seen for 3 (PDE6B, RD3, SPATA7). All LCA and ADRP cases were solved. Two ARRP cases had mutations in ADRP genes. 60% of ARRP cases remain unsolved. Phenotype-genotype correlation included a late onset, isolated, non-syndromic maculopathy associated with recessive BBS9 mutations, and coexistence of RPGR and C1QTNF5 mutations in ADRP.

Conclusions : This study highlights the cost effectiveness of the NGS platform to determine genetic diagnosis in this Māori and Polynesian IRD cohort. A definitive molecular diagnosis was possible in 57%, consistent with many populations recently described. The most prevalent mutation was in PDE6B, homozygously, suggesting a founder effect, and phenotype correlation now allows targeted and cost effective gene screening. A large number of novel changes were present. Recessive disease, particularly ARRP, still remains most elusive with nearly two thirds genetically undiagnosed, suggesting further novel molecular mechanisms are responsible for disease in this population. Knowledge of allele frequency in ethnic populations not represented in databases of human variation remains one of the most significant challenges when considering pathogenicity of observed variants.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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