Biallelic CPAMD8 Variants Are a Frequent Cause of Childhood and Juvenile Open-Angle Glaucoma.
Adolescent
Adult
Anterior Eye Segment
/ abnormalities
Child
Child, Preschool
Complement C3
/ genetics
Exome
/ genetics
Eye Abnormalities
/ genetics
Female
Gene Frequency
Glaucoma, Open-Angle
/ genetics
Humans
Hydrophthalmos
/ genetics
Infant
Infant, Newborn
Male
Pedigree
Phenotype
Polymorphism, Single Nucleotide
RNA
/ genetics
Retrospective Studies
Sequence Analysis, DNA
Trypsin Inhibitor, Kazal Pancreatic
/ genetics
Young Adult
alpha-Macroglobulins
/ genetics
Journal
Ophthalmology
ISSN: 1549-4713
Titre abrégé: Ophthalmology
Pays: United States
ID NLM: 7802443
Informations de publication
Date de publication:
06 2020
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
758-766Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.