June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Genetic analysis of Filipino families with hereditary cataract
Author Affiliations & Notes
  • Edward Ryan Collantes
    Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Harvard Medical School, Boston, Massachusetts, United States
  • Justine May Torregosa
    Cebu Institute of Medicine, Cebu City, Cebu, Philippines
  • Ma. Carmela Guevarra
    Cardinal Santos Medical Center, San Juan, Manila, Philippines
  • Michael Sibulo
    Saint Luke's Medical Center, Quezon City, Philippines
  • Lenard Paul Concepcion
    Tarlac Provincial Hospital, Tarlac City, Tarlac, Philippines
  • Christine Siguan-Bell
    Cebu Institute of Medicine, Cebu City, Cebu, Philippines
  • Maria Victoria Rondaris
    The Fred Hollows Foundation, Philippines
  • Shelley Ann Mangahas
    Tarlac Provincial Hospital, Tarlac City, Tarlac, Philippines
  • Manuel Delfin
    Manila Doctors Hospital, Manila, National Capital Region, Philippines
  • Janey L Wiggs
    Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Harvard Medical School, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Edward Ryan Collantes None; Justine May Torregosa None; Ma. Carmela Guevarra None; Michael Sibulo None; Lenard Paul Concepcion None; Christine Siguan-Bell None; Maria Victoria Rondaris None; Shelley Ann Mangahas None; Manuel Delfin None; Janey Wiggs None
  • Footnotes
    Support  NIH/NEI R01EY031820, P30EY014104
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1220. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Edward Ryan Collantes, Justine May Torregosa, Ma. Carmela Guevarra, Michael Sibulo, Lenard Paul Concepcion, Christine Siguan-Bell, Maria Victoria Rondaris, Shelley Ann Mangahas, Manuel Delfin, Janey L Wiggs; Genetic analysis of Filipino families with hereditary cataract. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1220.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Hereditary cataracts are an important cause of visual impairment especially in children. Variants in a number of genes are known to cause this condition. Here we report our findings in two Filipino families with hereditary cataract.

Methods : Twenty-eight members from four generations of Family 1 and 5 members from Family 2 were recruited. Subjects underwent a comprehensive eye exam and DNA samples were obtained.Whole exome and whole genome sequencing were performed in selected family members. The Whole Exome and Whole Genome Analysis Pipeline developed at the Broad Institute was used to align sequence reads,and do variant calling and annotation.Genomic data was examined for variants in genes known to cause hereditary cataract using the seqr platform. Sanger sequencing was done to confirm segregation of variants.

Results : A central star-like cataract with flecks was observed in 43 of 70 members of Family 1. The mean age of cataract surgery was at 33 years. A FLT (ferritin L-subunit) heterozygous missense 5’ UTR variant, c.-168G>C, was identified in all subjects with early-onset cataract.This variant has been previously reported as a cause of hyperferritinemia-cataract syndrome (HHCS) in European families and a similar mutation c.-167C>T has been reported in Chinese families.No systemic findings were identified. Serum ferritin levels were unavailable for mutation carriers. Three members of Family 2 were diagnosed with cataract at an average age of 1 month.A novel heterozygous missense variant, CRYGD c.391T>C (p.R340H) was identified in all affected family members. CRYGD encodes the gamma-4 crystallin protein, which accounts for approximately one-third of the total lens proteins.

Conclusions : In this study we identify the genetic cause of disease in two Filipino families with early-onset cataract. This is the first report of the FTL gene variant in Southeast Asia. Further investigation is needed to determine if the relatively older age of cataract surgery in Family 1 is a result of delayed consultation or if other genetic or environmental factors contribute to this disease spectrum.A comprehensive multisystem exam and serum ferritin levels is also warranted.The novel CRYGD variant adds to the list of pathogenic mutations associated with this gene. This study underscores the value of genetic investigations in previously unstudied populations to better define the genetic variation and also causes of disease from a global perspective.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

×
×

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.

×