PPIP5K2 and PCSK1 are Candidate Genetic Contributors to Familial Keratoconus

Mariam Lofty Khaled, Yelena Bykhovskaya, Chunfang Gu, Alice Liu, Michelle D. Drewry, Zhong Chen, Barbara A. Mysona, Emily Parker, Ryan P. McNabb, Hongfang Yu, Xiaowen Lu, Jing Wang, Xiaohui Li, Abdulrahman Al-Muammar, Jerome I. Rotter, Louise F. Porter, Amy Estes, Mitchell A. Watsky, Sylvia B. Smith, Hongyan XuKhaled K. Abu-Amero, Anthony Kuo, Stephen B. Shears, Yaron S. Rabinowitz, Yutao Liu

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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.

Original languageEnglish (US)
Article number19406
JournalScientific reports
Issue number1
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • General


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