Biallelic CPAMD8 Variants Are a Frequent Cause of Childhood and Juvenile Open-Angle Glaucoma
| Autor: | Lisa S. Kearns, Deepa A Taranath, Sandra E Staffieri, Angela J Chappell, Jillian Nicholl, James E. H. Smith, Emmanuelle Souzeau, Andrew Narita, Kathryn P. Burdon, James E. Elder, Tiger Zhou, Alex W. Hewitt, Jamie E Craig, Jonathan B Ruddle, David A. Mackey, Andrew Dubowsky, Shari Javadiyan, John Pater, Owen M. Siggs |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Pediatrics medicine.medical_specialty Adolescent Open angle glaucoma Glaucoma Polymorphism Single Nucleotide Young Adult Gene Frequency Anterior Eye Segment medicine Humans Exome alpha-Macroglobulins Eye Abnormalities Child Retrospective Studies Juvenile open angle Hydrophthalmos business.industry Infant Newborn Infant Complement C3 Sequence Analysis DNA medicine.disease Pedigree Eye abnormality Ophthalmology Phenotype Trypsin Inhibitor Kazal Pancreatic Alpha macroglobulins Child Preschool RNA Female business Glaucoma Open-Angle |
| Zdroj: | Ophthalmology. 127:758-766 |
| ISSN: | 0161-6420 |
| DOI: | 10.1016/j.ophtha.2019.12.024 |
| Popis: | Developmental abnormalities of the ocular anterior segment in some cases can lead to ocular hypertension and glaucoma. CPAMD8 is a gene of unknown function recently associated with ocular anterior segment dysgenesis, myopia, and ectopia lentis. We sought to assess the contribution of biallelic CPAMD8 variants to childhood and juvenile open-angle glaucoma.Retrospective, multicenter case series.A total of 268 probands and their relatives with a diagnosis of childhood or juvenile open-angle glaucoma.Developmental abnormalities of the ocular anterior segment in some cases can lead to ocular hypertension and glaucoma. CPAMD8 is a gene of unknown function recently associated with ocular anterior segment dysgenesis, myopia, and ectopia lentis. We sought to assess the contribution of biallelic CPAMD8 variants to childhood and juvenile open-angle glaucoma.Patients underwent a comprehensive ophthalmic assessment, with DNA from patients and their relatives subjected to genome, exome, or capillary sequencing. CPAMD8 RNA expression analysis was performed on tissues dissected from cadaveric human eyes.Diagnostic yield within a cohort of childhood and juvenile open-angle glaucoma, prevalence and risk of ophthalmic phenotypes, and relative expression of CPAMD8 in the human eye.We identified rare (allele frequency4×10Biallelic CPAMD8 variation was associated with a highly heterogeneous phenotype and in our cohorts was the second most common inherited cause of childhood glaucoma after CYP1B1 and juvenile open-angle glaucoma after MYOC. CPAMD8 sequencing should be considered in the investigation of both childhood and juvenile open-angle glaucoma, particularly when associated with iris abnormalities, cataract, or retinal detachment. |
| Databáze: | OpenAIRE |
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