PPIP5K2 and PCSK1 are Candidate Genetic Contributors to Familial Keratoconus.
Adult
Animals
Chromosome Mapping
Cornea
/ diagnostic imaging
Corneal Topography
/ methods
Disease Models, Animal
Female
Genetic Linkage
Genetic Predisposition to Disease
Genome, Human
/ genetics
Genotype
Humans
Keratoconus
/ genetics
Male
Mice
Mutation
/ genetics
Pedigree
Phosphotransferases (Phosphate Group Acceptor)
/ genetics
Proprotein Convertase 1
/ genetics
Quality of Life
Exome Sequencing
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
18 12 2019
18 12 2019
Historique:
received:
01
08
2019
accepted:
02
12
2019
entrez:
20
12
2019
pubmed:
20
12
2019
medline:
11
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31852976
doi: 10.1038/s41598-019-55866-5
pii: 10.1038/s41598-019-55866-5
pmc: PMC6920454
doi:
Substances chimiques
Phosphotransferases (Phosphate Group Acceptor)
EC 2.7.4.-
PPIP5K2 protein, human
EC 2.7.4.24
PCSK1 protein, human
EC 3.4.21.93
Proprotein Convertase 1
EC 3.4.21.93
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
19406Subventions
Organisme : NEI NIH HHS
ID : P30 EY005722
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)
ID : R01EY009052
Pays : International
Organisme : U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)
ID : R01EY028103
Pays : International
Organisme : NEI NIH HHS
ID : R01 EY021747
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY023242
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)
ID : R01EY024312
Pays : International
Organisme : NEI NIH HHS
ID : R01 EY009052
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)
ID : R01EY029302
Pays : International
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