<i>PPIP5K2</i> and <i>PCSK1</i> are Candidate Genetic Contributors to Familial Keratoconus

Khaled, Mariam Lofty, Bykhovskaya, Yelena, Gu, Chunfang, Liu, Alice, Drewry, Michelle D, Chen, Zhong, Mysona, Barbara A, Parker, Emily, McNabb, Ryan P, Yu, Hongfang
et al (show 15 more authors) (2019) <i>PPIP5K2</i> and <i>PCSK1</i> are Candidate Genetic Contributors to Familial Keratoconus. SCIENTIFIC REPORTS, 9 (1). 19406-.

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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.

Item Type: Article
Uncontrolled Keywords: Cornea, Animals, Humans, Mice, Keratoconus, Disease Models, Animal, Genetic Predisposition to Disease, Proprotein Convertase 1, Phosphotransferases (Phosphate Group Acceptor), Corneal Topography, Chromosome Mapping, Pedigree, Genotype, Mutation, Genome, Human, Quality of Life, Adult, Female, Male, Genetic Linkage, Exome Sequencing
Depositing User: Symplectic Admin
Date Deposited: 15 Jan 2020 10:08
Last Modified: 15 Apr 2024 10:07
DOI: 10.1038/s41598-019-55866-5
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3070652