Granular type I corneal dystrophy in a large consanguineous Tunisian family with homozygous p.R124S mutation in the TGFBI gene.

Détails

ID Serval
serval:BIB_B99FE7DB25FB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Granular type I corneal dystrophy in a large consanguineous Tunisian family with homozygous p.R124S mutation in the TGFBI gene.
Périodique
Ophthalmic genetics
Auteur(s)
Bouyacoub Y., Falfoul Y., Ouederni M., Sayeb M., Chedli A., Chargui M., Sassi H., Chakroun Chenguel I., Munier F.L., El Matri L., Abdelhak S., Cheour M.
ISSN
1744-5094 (Electronic)
ISSN-L
1381-6810
Statut éditorial
Publié
Date de publication
08/2019
Peer-reviewed
Oui
Volume
40
Numéro
4
Pages
329-337
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Purpose: We report the clinical features and the mutational analysis in a large Tunisian family with granular corneal dystrophy type I (GCD1). Patients and Methods: Thirty-three members of the Tunisian family underwent a complete ophthalmologic examination. DNA extraction and direct Sanger sequencing of the exons 4 and 12 of transforming growth factor β Induced (TGFBI) gene was performed for 42 members. For the molecular modeling of TGFBI protein, we used pGenTHREADER method to identify templates, 3D-EXPRESSO program to align sequences, MODELLER to get a homology model for the FAS1 (fasciclin-like) domains and finally NOMAD-ref web server for the energy minimization. Results: The diagnosis of GCD1 was clinically and genetically confirmed. Sequencing of exon 4 of TGFBI gene revealed the p.[R124S] mutation at heterozygous and homozygous states in patients with different clinical severities. Visual acuity was severely affected in the homozygous patients leading to a first penetrating keratoplasty. Recurrence occurred rapidly, began in the seat of the corneal stitches and remained superficial up to 40 years after the graft. For heterozygous cases, visual acuity ranged from 6/10 to 10/10. Corneal opacities were deeper and predominating in the stromal center. According to bioinformatic analysis, this mutation likely perturbs the protein physicochemical properties and reduces its solubility without structural modification. Conclusions: Our study describes for the first time phenotype-genotype correlation in a large Tunisian family with GCDI and illustrates for the first time clinical and histopathological presentation of homozygous p.[R124S] mutation. These results help to understand pathophysiology of the disease.
Mots-clé
gene, Granular corneal dystrophy type I, Tunisian family, homozygosity, incomplete dominance, recurrence, gene
Pubmed
Web of science
Création de la notice
04/08/2019 15:10
Dernière modification de la notice
16/10/2019 5:13
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