PPIP5K2 and PCSK1 are Candidate Genetic Contributors to Familial Keratoconus
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.
Abstract
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…