July 2018
Volume 59, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2018
Comprehensive Genetic Testing Identifies Rare Pathogenic Variants for Anterior Segment Dysgenesis
Author Affiliations & Notes
  • Dayna Morel
    Department of Human Genetics, University of Miami, Miami, Florida, United States
  • Saradadevi Thanikachalam
    John P.Husmann Institute for Human Genomics, University of Miami, Miami, Florida, United States
  • Elizabeth Hodapp
    Bascom Palmer Eye Institute, University of Miami, Miami, Florida, United States
  • Ta Chen Chang
    Bascom Palmer Eye Institute, University of Miami, Miami, Florida, United States
  • F. Basak Cengiz
    John P.Husmann Institute for Human Genomics, University of Miami, Miami, Florida, United States
  • Guney Bademci
    John P.Husmann Institute for Human Genomics, University of Miami, Miami, Florida, United States
  • William Scott
    John P.Husmann Institute for Human Genomics, University of Miami, Miami, Florida, United States
  • Alana Grajewski
    Bascom Palmer Eye Institute, University of Miami, Miami, Florida, United States
  • Mustafa Tekin
    John P.Husmann Institute for Human Genomics, University of Miami, Miami, Florida, United States
    Department of Human Genetics, University of Miami, Miami, Florida, United States
  • Footnotes
    Commercial Relationships   Dayna Morel, None; Saradadevi Thanikachalam, None; Elizabeth Hodapp, None; Ta Chang, Clinical Decisions in Glaucoma, 2nd Edition (F); F. Basak Cengiz, None; Guney Bademci, None; William Scott, None; Alana Grajewski, None; Mustafa Tekin, None
  • Footnotes
    Support  The Samuel and Ethel Balkan International Pediatric Glaucoma Center
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 6048. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Dayna Morel, Saradadevi Thanikachalam, Elizabeth Hodapp, Ta Chen Chang, F. Basak Cengiz, Guney Bademci, William Scott, Alana Grajewski, Mustafa Tekin; Comprehensive Genetic Testing Identifies Rare Pathogenic Variants for Anterior Segment Dysgenesis. Invest. Ophthalmol. Vis. Sci. 2018;59(9):6048.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Anterior segment dysgenesis (ASD) comprises a wide spectrum of ocular anomalies of the cornea, iris, and lens. ASD may involve only the eye or may be part of a systemic syndrome. Causative variants in eight genes have been identified in isolated ASD. Over 40 syndromes include ASD as a finding. In this study, we aim to reveal DNA variants in known and novel genes underlying various types of ASD in order to better define the spectrum of causative variants.

Methods : Probands from 34 unrelated families and their available first degree relatives were included. In 10 probands with isolated ASD, we screened mutations in known ASD genes via next-generation sequencing gene panels. In the remaining 24 probands with isolated or syndromic ASD, we performed whole exome sequencing. We analyzed the next-generation sequencing data for single nucleotide variants, small indels and copy number variants. Sanger sequencing was used to confirm variants and evaluate their segregation in available family members.

Results : Overall, we identified 16 rare and likely causative variants (6 novel) in 13 of the families (38%). Each variant was observed only in one family. Single nucleotide variants and small indels in isolated ASD genes include those in FOXC1 (4 families heterozygous; 1 novel), CYP1B1 (2 families; 1 family homozygous and 1 family compound heterozygous), PXDN (1 family compound heterozygous; 2 novel), FOXE3 (1 family homozygous; novel), and PAX6 (1 family heterozygous). In addition, a child with bilateral aniridia and glaucoma is heterozygous for a large deletion including PAX6. Syndromic ASD genes with causative variants are BMP4 (syndromic microphthalmia 6; 1 family heterozygous; novel), B3GLCT (Peters Plus syndrome; 1 family compound heterozygous; 1 novel) and GJA1 (oculodentodigital dysplasia; 1 family heterozygous). One patient with Peters anomaly is compound heterozygous for two PXDN variants; causative variants in PXDN have not previously been reported in this condition. Further analysis for variants in novel genes is ongoing.

Conclusions : Comprehensive analysis of DNA variants via next-generation sequencing allows us to search for causative variants in known genes with an advantage of whole exome sequencing to include potential novel genes. Underlying genetic causes of ASD are very heterogeneous; only less than half can be detected in known genes.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×