PPIP5K2 and PCSK1 are Candidate Genetic Contributors to Familial Keratoconus
| Autor: | Chunfang Gu, Anthony N. Kuo, Zhong Chen, Hongfang Yu, Alice Liu, Amy Estes, Hongyan Xu, Mariam Lofty Khaled, Abdulrahman Al-Muammar, Louise F. Porter, Stephen B. Shears, Jing Wang, Yutao Liu, Mitchell A. Watsky, Khaled K. Abu-Amero, Yaron S. Rabinowitz, Jerome I. Rotter, Yelena Bykhovskaya, Xiaowen Lu, Ryan P. McNabb, Sylvia B. Smith, Emily J. Parker, Xiaohui Li, Barbara A. Mysona, Michelle Drewry |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Pathology genetic structures Genetic Linkage lcsh:Medicine Eye Whole Exome Sequencing Pathogenesis Cornea Mice 0302 clinical medicine Genetics research 2.1 Biological and endogenous factors Medicine Aetiology lcsh:Science Exome Multidisciplinary Genome Chromosome Mapping Phenotype 3. Good health Pedigree Experimental models of disease Proprotein Convertase 1 Vision disorders Female Biotechnology Human Adult Keratoconus medicine.medical_specialty Genotype Corneal diseases Article Novel gene 03 medical and health sciences Rare Diseases Clinical Research Exome Sequencing Genetics Animals Humans Genetic Predisposition to Disease Eye Disease and Disorders of Vision Gene Pathological Phosphotransferases (Phosphate Group Acceptor) business.industry Genome Human Animal Human Genome lcsh:R Phosphotransferases Corneal Topography Corneal tomography medicine.disease eye diseases Disease Models Animal 030104 developmental biology Disease Models Mutation 030221 ophthalmology & optometry Quality of Life lcsh:Q sense organs business |
| Zdroj: | Scientific reports, vol 9, iss 1 SCIENTIFIC REPORTS Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-16 (2019) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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