Biallelic CPAMD8 Variants Are a Frequent Cause of Childhood and Juvenile Open-Angle Glaucoma.


Journal

Ophthalmology
ISSN: 1549-4713
Titre abrégé: Ophthalmology
Pays: United States
ID NLM: 7802443

Informations de publication

Date de publication:
06 2020
Historique:
received: 16 07 2019
revised: 19 12 2019
accepted: 20 12 2019
pubmed: 23 2 2020
medline: 15 12 2020
entrez: 23 2 2020
Statut: ppublish

Résumé

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 frequency < 4×10 Biallelic 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.

Identifiants

pubmed: 32085876
pii: S0161-6420(19)32377-2
doi: 10.1016/j.ophtha.2019.12.024
pii:
doi:

Substances chimiques

CPAMD8 protein, human 0
Complement C3 0
alpha-Macroglobulins 0
Trypsin Inhibitor, Kazal Pancreatic 50936-63-5
RNA 63231-63-0

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

758-766

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Auteurs

Owen M Siggs (OM)

Department of Ophthalmology, Flinders University, Adelaide, Australia. Electronic address: owen.siggs@flinders.edu.au.

Emmanuelle Souzeau (E)

Department of Ophthalmology, Flinders University, Adelaide, Australia. Electronic address: emmanuelle.souzeau@flinders.edu.au.

Deepa A Taranath (DA)

Department of Ophthalmology, Flinders University, Adelaide, Australia.

Andrew Dubowsky (A)

SA Pathology, Adelaide, Australia.

Angela Chappell (A)

Department of Ophthalmology, Flinders University, Adelaide, Australia.

Tiger Zhou (T)

Department of Ophthalmology, Flinders University, Adelaide, Australia.

Shari Javadiyan (S)

Department of Ophthalmology, Flinders University, Adelaide, Australia.

Jillian Nicholl (J)

SA Pathology, Adelaide, Australia.

Lisa S Kearns (LS)

Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.

Sandra E Staffieri (SE)

Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia; Department of Ophthalmology, University of Melbourne, Melbourne, Australia; Department of Ophthalmology, Royal Children's Hospital, Melbourne, Australia.

Andrew Narita (A)

Geelong Eye Centre, Geelong, Australia.

James E H Smith (JEH)

Department of Ophthalmology, Children's Hospital at Westmead, Sydney, Australia; Discipline of Ophthalmology, University of Sydney, Sydney, Australia; Department of Ophthalmology, Macquarie University, Sydney, Australia.

John Pater (J)

Department of Ophthalmology, Flinders University, Adelaide, Australia.

Alex W Hewitt (AW)

Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia; Department of Ophthalmology, University of Melbourne, Melbourne, Australia; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.

Jonathan B Ruddle (JB)

Department of Ophthalmology, University of Melbourne, Melbourne, Australia; Department of Ophthalmology, Royal Children's Hospital, Melbourne, Australia.

James E Elder (JE)

Department of Ophthalmology, University of Melbourne, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia.

David A Mackey (DA)

Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia; Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, Australia.

Kathryn P Burdon (KP)

Department of Ophthalmology, Flinders University, Adelaide, Australia; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.

Jamie E Craig (JE)

Department of Ophthalmology, Flinders University, Adelaide, Australia.

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Classifications MeSH