Transforming growth factor beta-induced p.(L558P) variant is associated with autosomal dominant lattice corneal dystrophy type IV in a large cohort of Spanish patients.
Adult
Aged
Aged, 80 and over
Contrast Sensitivity
/ physiology
Corneal Dystrophies, Hereditary
/ diagnosis
DNA Mutational Analysis
Exons
/ genetics
Extracellular Matrix Proteins
/ genetics
Female
Genetic Association Studies
Genetic Variation
Humans
Male
Mesopic Vision
/ physiology
Middle Aged
Pedigree
Retrospective Studies
Slit Lamp Microscopy
Tomography, Optical Coherence
Transforming Growth Factor beta
/ genetics
Young Adult
clinical genetics
corneal dystrophy
genetic analysis
Journal
Clinical & experimental ophthalmology
ISSN: 1442-9071
Titre abrégé: Clin Exp Ophthalmol
Pays: Australia
ID NLM: 100896531
Informations de publication
Date de publication:
Sep 2019
Sep 2019
Historique:
received:
27
12
2018
revised:
18
03
2019
accepted:
30
04
2019
pubmed:
6
5
2019
medline:
21
10
2020
entrez:
7
5
2019
Statut:
ppublish
Résumé
Rare transforming growth factor beta-induced (TGFBI) gene variants are involved in autosomal dominant corneal dystrophies (CDs) with heterogeneous clinical features. The purpose of this study was to analyse TGFBI gene variants and genotype-phenotype correlations in a cohort affected by atypical stromal CD. Retrospective cohort study (from May 2014 to September 2017). Thirty-five individuals from 10 unrelated South European families presenting atypical lattice CD (LCD) were included. Corneal phenotypes were assessed by slit-lamp examination and optical coherence tomography (OCT). Contrast sensitivity was measured under mesopic conditions. Genomic DNA was obtained from blood samples, and all 17 TGFBI exons were screened for variants by Sanger sequencing. p.(L558P) variant of TGFBI gene. The p.(L558P) variant was identified in 22 members of the 10 families diagnosed with atypical LCD, characterized by late-onset and absence of recurrent erosion syndrome. OCT revealed punctiform deposits in the deep-mid stroma and normal anterior stroma. This variant was demonstrated to be transmitted with the disease according to autosomal dominant inheritance in most families. To the best of our knowledge, we describe a detailed clinical characterization of the largest CD cohort carrying the TGFBI p.(L558P) variant. We propose that the atypical phenotype of this recently reported alteration can be classified as a form of LCD type IV. The results show that OCT and anterior-posterior analysis of the stromal location of the opacities, along with a genetic analysis of TGFBI, are required to ensure accurate diagnosis and management of CDs.
Sections du résumé
IMPORTANCE
OBJECTIVE
Rare transforming growth factor beta-induced (TGFBI) gene variants are involved in autosomal dominant corneal dystrophies (CDs) with heterogeneous clinical features.
BACKGROUND
BACKGROUND
The purpose of this study was to analyse TGFBI gene variants and genotype-phenotype correlations in a cohort affected by atypical stromal CD.
DESIGN
METHODS
Retrospective cohort study (from May 2014 to September 2017).
PARTICIPANTS
METHODS
Thirty-five individuals from 10 unrelated South European families presenting atypical lattice CD (LCD) were included.
METHODS
METHODS
Corneal phenotypes were assessed by slit-lamp examination and optical coherence tomography (OCT). Contrast sensitivity was measured under mesopic conditions. Genomic DNA was obtained from blood samples, and all 17 TGFBI exons were screened for variants by Sanger sequencing.
MAIN OUTCOME MEASURES
METHODS
p.(L558P) variant of TGFBI gene.
RESULTS
RESULTS
The p.(L558P) variant was identified in 22 members of the 10 families diagnosed with atypical LCD, characterized by late-onset and absence of recurrent erosion syndrome. OCT revealed punctiform deposits in the deep-mid stroma and normal anterior stroma. This variant was demonstrated to be transmitted with the disease according to autosomal dominant inheritance in most families.
CONCLUSIONS AND RELEVANCE
CONCLUSIONS
To the best of our knowledge, we describe a detailed clinical characterization of the largest CD cohort carrying the TGFBI p.(L558P) variant. We propose that the atypical phenotype of this recently reported alteration can be classified as a form of LCD type IV. The results show that OCT and anterior-posterior analysis of the stromal location of the opacities, along with a genetic analysis of TGFBI, are required to ensure accurate diagnosis and management of CDs.
Substances chimiques
Extracellular Matrix Proteins
0
Transforming Growth Factor beta
0
betaIG-H3 protein
148710-76-3
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
871-880Informations de copyright
© 2019 Royal Australian and New Zealand College of Ophthalmologists.
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