July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Diagnostic genetic testing using whole exome sequencing in Filipino families with early-onset glaucoma
Author Affiliations & Notes
  • Edward Ryan Collantes
    Harvard Medical School, Mass Eye and Ear, Cambridge, Massachusetts, United States
    Department of Ophthalmology, Manila Doctors Hospital , Manila, Philippines
  • Baojian Fan
    Harvard Medical School, Mass Eye and Ear, Cambridge, Massachusetts, United States
  • Kevin Linkroum
    Harvard Medical School, Mass Eye and Ear, Cambridge, Massachusetts, United States
  • Janey L Wiggs
    Harvard Medical School, Mass Eye and Ear, Cambridge, Massachusetts, United States
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5153. doi:
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    • Get Citation

      Edward Ryan Collantes, Baojian Fan, Kevin Linkroum, Janey L Wiggs; Diagnostic genetic testing using whole exome sequencing in Filipino families with early-onset glaucoma. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5153.

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

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Abstract

Purpose : Glaucoma developing before age 40 is defined as early-onset and includes primary congenital glaucoma,anterior segment dysgenesis and juvenile open angle glaucoma.Currently, 9 genes are known to cause various types of early-onset glaucoma and identifying mutations in affected patients can inform genetic counseling and risk assessment.Previously we identified a novel MYOC mutation in patients from an isolated region of the Philippines suggesting that this population could benefit from genetic testing.To determine the feasibility of genetic testing in remote areas we completed a pilot study of early-onset Filipino glaucoma cases

Methods : Three Filipino families with a child affected by early-onset glaucoma were recruited.After informed consent,a comprehensive eye exam was done and DNA samples obtained for the affected child and unaffected family members.Whole exome sequencing (WES) was performed using the Agilent SureSelect Human All Exon v6 and the Illumina HiSeq 2000.The Ocular Genomics Institute WES pipeline was used to align sequence reads and complete variant calling and annotation.Average coverage was 105× for 99% of coding sequences

Results : The WES data was examined for mutations in genes known to cause early-onset glaucoma:CYP1B1,LTBP2,MYOC,FOXC1,PITX2,PAX6,TEK,OPTN,TBK1.Disease-causing mutations were expected to be rare, disrupt protein function, and have high estimates of pathogenicity (SIFT, Polyphen2).A DNA variant with the properties expected for a disease-causing mutation was identified in one case in PAX6 (p.Tyr296*).Disease-causing mutations in any of the known early-onset glaucoma genes were not identified in the remaining 2 cases.Analysis of the WES data for the unsolved cases and family members identified several genes with interesting variants for further investigation: DDB1,DNAH5,DRAP1,FBXO40,IGSF10,IL7R,LRRC15,PAAF1 and STXBP5L

Conclusions : Diagnostic genetic testing using WES can successfully identify disease-causing mutations for early-onset glaucoma cases from remote populations.In this small pilot study we identified a disease-causing mutation in one of three cases, a diagnostic yield similar to that observed in other populations.The absence of mutations in known genes in the remaining cases suggests that early-onset glaucoma is genetically heterogeneous and that further study using WES and other genomic methods is likely to identify novel early-onset glaucoma genes

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

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