June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Identification of novel variants in CYP1B1, PITX2, FOXC1, and PAX6 in congenital glaucoma and anterior segment dysgenesis
Author Affiliations & Notes
  • Shazia Micheal
    Clinical Genetics, Academic Medical Centre, Amsterdam, Netherlands
    Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center , Nijmegen, Netherlands
  • Sorath Noorani Siddiqui
    Pediatric Ophthalmology, Al-Shifa Eye Trust Hospital Jhelum Road, Rawalpindi, Pakistan
  • Saemah Nuzhat Zafar
    Pediatric Ophthalmology, Al-Shifa Eye Trust Hospital Jhelum Road, Rawalpindi, Pakistan
  • Ralph J. Florijn
    Clinical Genetics, Academic Medical Centre, Amsterdam, Netherlands
  • Hennie Bikker
    Clinical Genetics, Academic Medical Centre, Amsterdam, Netherlands
  • Camiel J F Boon
    Leiden University Medical Center, Leiden, Netherlands
  • Muhammad Khan
    Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands
  • Anneke I Den Hollander
    Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center , Nijmegen, Netherlands
    Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands
  • Arthur Bergen
    Clinical Genetics, Academic Medical Centre, Amsterdam, Netherlands
  • Footnotes
    Commercial Relationships   Shazia Micheal, None; Sorath Siddiqui , None; Saemah Zafar , None; Ralph J. Florijn, None; Hennie Bikker, None; Camiel Boon, None; Muhammad Khan, None; Anneke Den Hollander, None; Arthur Bergen, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2124. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Shazia Micheal, Sorath Noorani Siddiqui, Saemah Nuzhat Zafar, Ralph J. Florijn, Hennie Bikker, Camiel J F Boon, Muhammad Khan, Anneke I Den Hollander, Arthur Bergen; Identification of novel variants in CYP1B1, PITX2, FOXC1, and PAX6 in congenital glaucoma and anterior segment dysgenesis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2124.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : The current study was undertaken to identify the pathogenic mutations in the CYP1B1, PAX6, PITX2 and FOXC1 among the families and sporadic patients with primary congenital glaucoma and anterior segment dysgenesis which includes Axenfeld Rieger syndrome and aniridia.

Methods : The study included a cohort of probands of Pakistani families (n=80) diagnosed with PCG. A European cohort included PCG; (n=97; 4 families, 93 sporadic), Axenfeld Rieger syndrome (ARS; n=50) and aniridia (n=42; 11 families, 31 sporadic patients). Complete ophthalmic examination was performed for all the affected and unaffected family members and sporadic patients. Total genomic DNA was isolated from the peripheral blood and was used for the genetic analysis. PCR and Sanger sequencing were performed for the exons and intron-exon boundaries of the associated genes. In addition, MLPA was used to identify the deletions in the PAX6 in patients with aniridia.

Results : A total of 12 pathogenic CYP1B1 variants (including two novel mutations c.1044-1G>C & p.Ser464Thr) have been identified which co-segregated with the disease in the 25 Pakistani families. In two families, compound heterozygous mutations (p.Arg368His/p.Arg444*; p.Arg390His/p.Ser464Thr) were identified. In the European cohort, 15 CYP1B1 mutations have been identified, that included one novel variant (c.475C>T:p.Gln159*). In total CYP1B1 explains 31.25% of Pakistani and 27.8% of the European cohort however, 7.2% of the European cases revealed only single mutated allele and the other variant remained undetermined.

The FOXC1 & PITX2 genes explains 10% and 6% ARS cases respectively. Identified variants include 4 novel FOXC1 mutations (p.Gln200Argfs*109, p. Arg127Cys, P.Arg169Gln and p.Gly378_Gly380del) and three PITX2 novel mutations (p.Tyr109*, p.Thr122Pro and c.391-11A>G). In total 27 mutations were identified in the PAX6 gene (18 unique and 9 known) in the families and the sporadic patients with aniridia. Eleven families and 24 of 31 (77.4%) sporadic patients were solved with PAX6. Several mutations identified in the PAX6 among the families were de novo.

Conclusions : In summary, the identification of novel mutations in the current study expands the mutational spectrum of the CYP1B1 gene in the PCG patients and PITX2, FOXC1 and PAX6 in patients with ARS and aniridia respectively.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

×
×

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.

×