Zonule-Associated Gene Variants in Isolated Ectopia Lentis and Glaucoma.
Journal
Journal of glaucoma
ISSN: 1536-481X
Titre abrégé: J Glaucoma
Pays: United States
ID NLM: 9300903
Informations de publication
Date de publication:
01 07 2023
01 07 2023
Historique:
received:
19
11
2022
accepted:
05
02
2023
medline:
30
6
2023
pubmed:
23
3
2023
entrez:
22
3
2023
Statut:
ppublish
Résumé
We report 3 novel variants in fibrillin-1 (FBN1) and latent transforming growth factor-β-binding protein 2 (LTBP2) in 3 families with isolated ectopia lentis (EL), which shed new light on the diagnosis and genetic counseling of EL and secondary glaucoma in clinical settings. To explore the genetic mechanism in 3 families with isolated EL and secondary angle closure glaucoma. Three Han Chinese families with EL and glaucoma were recruited. All of the participants underwent complete ocular and general physical examinations and DNA samples were extracted from peripheral venous blood and screened for disease-causing variants using whole exome and Sanger sequencing. In silico analyses were performed to predict the structural and functional changes in gene variants and abnormal proteins. All 3 probands presented with EL and pupillary-blocking glaucoma. Genetic testing showed that all the patients have zonule-related gene mutations, with the proband (II:1), as well as his mother (I:2) and daughters (III:1 and III:2) from family 1 carrying a heterozygous mutation in FBN1 gene (c.6493G>T:p.(V2165L)); the proband (II:1) from family 2 carrying a heterozygous mutation in FBN1 gene (c.2543C>A:p.(T848N)), and the proband (II:1) from family 3 carrying a pair of compound heterozygous mutations in LTBP2 gene (c.4825T>A:p.(C1609S) / c.529T>C:p.(W177R)). No other genetic variants were found to be associated with the phenotypes of patients and other family members in this study. All variants are predicted to affect the structure and function of proteins as risk factors for EL based on bioinformatics analysis. Four novel mutations were identified in 3 families with EL, suggesting an intimate link between specific mutations in FBN1 and LTBP2 and isolated EL and angle closure glaucoma. Our results expanded the variant spectrum of zonule-related genes and helped explore the underlying molecular pathology of these disorders.
Identifiants
pubmed: 36946977
doi: 10.1097/IJG.0000000000002209
pii: 00061198-202307000-00012
doi:
Substances chimiques
Fibrillins
0
Microfilament Proteins
0
Fibrillin-1
0
LTBP2 protein, human
0
Latent TGF-beta Binding Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e80-e89Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Disclosure: The authors declare no conflict of interest.
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