July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Five novel ZEB1 mutations including a 0.34 Mb deletion detected by whole genome sequencing in patients with posterior polymorphous corneal dystrophy type 3
Author Affiliations & Notes
  • Petra Liskova
    Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia
    Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia
  • Lubica Dudakova
    Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia
  • Cerys J. Evans
    UCL Institute of Ophthalmology, London, United Kingdom
  • Pavlina Skalicka
    Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia
  • Nikolas Pontikos
    UCL Genetics Institute, London, United Kingdom
  • Ales Horinek
    Institute of Biology and Human Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia
  • Tomas Kubena
    Ophthalmology Clinic of Dr. Tomas Kubena, Zlin, Czechia
  • Alice Davidson
    UCL Institute of Ophthalmology, London, United Kingdom
  • Alison J Hardcastle
    UCL Institute of Ophthalmology, London, United Kingdom
  • Stephen J. Tuft
    Moorfields Eye Hospital, London, United Kingdom
  • Footnotes
    Commercial Relationships   Petra Liskova, None; Lubica Dudakova, None; Cerys Evans, None; Pavlina Skalicka, None; Nikolas Pontikos, None; Ales Horinek, None; Tomas Kubena, None; Alice Davidson, None; Alison Hardcastle, None; Stephen Tuft, None
  • Footnotes
    Support  This work was supported by GACR 17-12355S, UNCE 204011 and PROGRES-Q26/LF1. PS was supported by GAUK 364/2017 and SVV 260367/2017.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2917. doi:
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      Petra Liskova, Lubica Dudakova, Cerys J. Evans, Pavlina Skalicka, Nikolas Pontikos, Ales Horinek, Tomas Kubena, Alice Davidson, Alison J Hardcastle, Stephen J. Tuft; Five novel ZEB1 mutations including a 0.34 Mb deletion detected by whole genome sequencing in patients with posterior polymorphous corneal dystrophy type 3. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2917.

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

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Abstract

Purpose : To report on clinical and molecular genetic findings in six families diagnosed with posterior polymorphous corneal dystrophy.

Methods : Ocular examination, Sanger sequencing of ZEB1 coding regions in all probands and whole genome sequencing in one proband was performed. Sanger sequencing was used to verify breakpoints and for segregation within the families.

Results : Five novel heterozygous ZEB1 mutations were detected confirming a diagnosis of PPCD type 3; a deletion chr10.hg19:31,476,839_31,812,954, and point mutations c.646G>T, p.(Glu216*); c.1669C>T, p.(Gln557*); c.2577del, p.(Val860*); c.1918C>T, p.(Gln640*). In addition, de novo occurrence of a previously reported mutation c.689_690del; p.(His230Arg*7) was found in one patient. Clinical variability ranged from minimal corneal findings in one asymptomatic carrier with bilateral uncorrected visual acuity of 1.0, to a more severe phenotype, observed in 6 (60%) eyes out of 10 with best corrected visual acuity of < 0.5. Non-keratoconic corneal steepening (mean keratometry ≥ 46.75 D) was detected in 5 (56%) eyes out of 9. Endothelial cell density was decreased in all 5 eyes with available measurements (range 751-1584 cells/mm2). One 23-year-old male had cloudy corneas at 6 weeks of age and marked corneal shape asymmetry with a mean keratometry of 39.8 D in the right eye and 50.5 D in the left eye. Except for hydrocele in one male, no other systemic findings were noted.

Conclusions : PPCD3 may be associated with impaired postnatal corneal development. The occurrence of recurrent mutations in ZEB1 is rare, to date only two have been documented, and the proportion of patients with PPCD3 is currently underestimated.

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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