July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Homozygous Mutation in the ELMO3 Gene with Keratoconus
Author Affiliations & Notes
  • Mariam Lotfy Khaled
    Department of Cell Biology and Anatomy, Augusta University, Augusta, Georgia, United States
  • Khaled Abu-Amero
    Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  • Abdulrahman Al-Muammar
    Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  • Yelena Bykhovskaya
    Department of Surgery, Regenerative Medicine Institute, Los Angeles , California, United States
  • Xiaoyo Gao
    Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Michael A Hauser
    Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States
  • R. Rand Allingham
    Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States
  • Yaron Rabinowitz
    Department of Surgery, Regenerative Medicine Institute, Los Angeles , California, United States
  • Yutao Liu
    Department of Cell Biology and Anatomy, Augusta University, Augusta, Georgia, United States
    James & Jean Culver Vision Discovery Institute, Augusta University, Augusta, Georgia, United States
  • Footnotes
    Commercial Relationships   Mariam Khaled, None; Khaled Abu-Amero, None; Abdulrahman Al-Muammar, None; Yelena Bykhovskaya, None; Xiaoyo Gao, None; Michael Hauser, None; R. Rand Allingham, None; Yaron Rabinowitz, None; Yutao Liu, None
  • Footnotes
    Support  National Institute of Health grant R01 EY023242 (Yutao Liu), P30-EY005722 to Duke Eye Center, King Saud University in Saudi Arabia, and Medical College of Georgia at Augusta University (Augusta, GA).
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 743. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Mariam Lotfy Khaled, Khaled Abu-Amero, Abdulrahman Al-Muammar, Yelena Bykhovskaya, Xiaoyo Gao, Michael A Hauser, R. Rand Allingham, Yaron Rabinowitz, Yutao Liu; Homozygous Mutation in the ELMO3 Gene with Keratoconus. Invest. Ophthalmol. Vis. Sci. 2018;59(9):743.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Keratoconus (KC) is a corneal thinning disorder and a leading cause of corneal transplantation worldwide. Mutations in MIR184 and other genes account for less than 10% KC patients. However, the majority of the mutations remains to be identified. We aimed to identify novel genetic mutations in a Saudi Arabic KC-affected family.

Methods : A two-generation consanguineous Saudi Arabic family was found with autosomal recessive inheritance. This family included two unaffected parents, 3 unaffected daughters, 3 affected sons, and one affected daughter. We performed whole exome sequencing (WES) with 5 subjects, including both unaffected parents and three children (two affected males and one unaffected female). WES was done using Roche NimbleGen SeqCap EZ Exome Library 3.0 with a 64 Mb sequence capture with 100bp paired-end sequencing with Illumina HiSeq sequencers. After quality control, sequence alignment was done with the BWA algorithm and variants were annotated using GATK. We used SVS8 software to filter and prioritize variants based on the following criteria: 1) good quality and read depth, 2) show recessive inheritance mode, 3) minor allele frequency (MAF) < 0.1% in publically available variant databases (The Exome Aggregation Consortium (ExAC), NHLBI GO Exome Sequencing Project (ESP), and 1000 Genomes), 4) exonic, non-synonymous variants. PCR-based Sanger sequencing was used to validate selected variants in all family members.

Results : We identified 3 missense single nucleotide variants (SNVs) in 3 genes: MCM6 (rs55660827, c.2428T>C, p.Tyr810His), ELMO3 (rs183146864, c.1009G>A, p.Val337Ile), and MYOCD (rs200094820, c.1234G>C, Val412Leu). In silico functional prediction algorithms (SIFT, Polyphen2, MutationTaster, and MutationAssessor) suggest SNVs in MCM6 and ELMO3 to be pathogenic; however, MYOCD SNV to be benign. In the Greater Middle East (GME) Variome database, MCM6 SNV is common (MAF = 0.094), ELMO3 SNV is uncommon with MAF = 0.015 (one homozygote out of 993 individuals), and MYOCD SNV is rare (MAF = 0.0065). Our RNA-Seq data from normal human corneas (n=9) showed moderate to high expression of ELMO3 and MCM6, but low expression of MYOCD. Mice with homozygous loss of ELMO3 are reported to have corneal opacity, indicating a potential role of ELMO3 in cornea function.

Conclusions : The homozygous mutation in the ELMO3 gene (rs183146864) might be causative in the Saudi Arabic family affected with KC.

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.

×