PPIP5K2 and PCSK1 are Candidate Genetic Contributors to Familial Keratoconus

Journal Article

2019

Published in: https://www.nature.com/articles/s41598-019-55866-5

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.

• Magazine \ Newspaper: Nature