@article{32a27eb799d6405fa18a5d74b3bd0524,
title = "PPIP5K2 and PCSK1 are Candidate Genetic Contributors to Familial Keratoconus",
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 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.",
author = "Khaled, {Mariam Lofty} and Yelena Bykhovskaya and Chunfang Gu and Alice Liu and Drewry, {Michelle D.} and Zhong Chen and Mysona, {Barbara A.} and Emily Parker and McNabb, {Ryan P.} and Hongfang Yu and Xiaowen Lu and Jing Wang and Xiaohui Li and Abdulrahman Al-Muammar and Rotter, {Jerome I.} and Porter, {Louise F.} and Amy Estes and Watsky, {Mitchell A.} and Smith, {Sylvia B.} and Hongyan Xu and Abu-Amero, {Khaled K.} and Anthony Kuo and Shears, {Stephen B.} and Rabinowitz, {Yaron S.} and Yutao Liu",
note = "Funding Information: We acknowledge the Electron Microscopy and Histology Core laboratory at Augusta University for processing mouse corneas. We acknowledge the kind support from Xuezhi Cui at Dr. Sylvia Smith{\textquoteright}s laboratory for the usage of immunofluorescence microscope and OCT system. We sincerely thank all the donors and families for participation. This study would not be feasible without these precious samples. We thank The Glaucoma Foundation, The Glaucoma Research Foundation, The BrightFocus Foundation, The Eye Defects Research Foundation, NIH R01EY023242 (YL), R21EY028671 (YL), R01EY009052 (YSR), R01EY021747 (MAW), R01EY028103 (SBS), R01EY024312 (ANK), R01EY029302 (ANK), P30EY005722 (Duke University Eye Center) for their financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41598-019-55866-5",
language = "English (US)",
volume = "9",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Research",
number = "1",
}