PPIP5K2 and PCSK1 are Candidate Genetic Contributors to Familial Keratoconus.

Journal Article (Journal Article)

Keratoconus (KC) is the most common corneal ectatic disorder affecting >300,000 people in the US. KC normally has its onset in adolescence, progressively worsening through the third to fourth decades of life. KC patients report significant impaired vision-related quality of life. Genetic factors play an important role in KC pathogenesis. To identify novel genes in familial KC patients, we performed whole exome and genome sequencing in a four-generation family. We identified potential variants in the PPIP5K2 and PCSK1 genes. Using in vitro cellular model and in vivo gene-trap mouse model, we found critical evidence to support the role of PPIP5K2 in normal corneal function and KC pathogenesis. The gene-trap mouse showed irregular corneal surfaces and pathological corneal thinning resembling KC. For the first time, we have integrated corneal tomography and pachymetry mapping into characterization of mouse corneal phenotypes which could be widely implemented in basic and translational research for KC diagnosis and therapy in the future.

Full Text

Duke Authors

Cited Authors

  • Khaled, ML; Bykhovskaya, Y; Gu, C; Liu, A; Drewry, MD; Chen, Z; Mysona, BA; Parker, E; McNabb, RP; Yu, H; Lu, X; Wang, J; Li, X; Al-Muammar, A; Rotter, JI; Porter, LF; Estes, A; Watsky, MA; Smith, SB; Xu, H; Abu-Amero, KK; Kuo, A; Shears, SB; Rabinowitz, YS; Liu, Y

Published Date

  • December 18, 2019

Published In

Volume / Issue

  • 9 / 1

Start / End Page

  • 19406 -

PubMed ID

  • 31852976

Pubmed Central ID

  • PMC6920454

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/s41598-019-55866-5


  • eng

Conference Location

  • England