Variant lattice corneal dystrophy associated with compound heterozygous mutations in the<i>TGFBI</i>gene

Ann, Lydia; Abbouda, Alessandro; Frausto, Ricardo F.; Huseynli, Samira; Gupta, Kishan; Alió, Jorge L.; Aldave, Anthony J.

doi:10.1136/bjophthalmol-2015-307602

Cited by 11 publications

(27 citation statements)

References 17 publications

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“…20, 21 In the Mexican family, two common SNPs were identified in all affected individuals screened, with an allele frequency significantly higher than that in the population. However, as these SNPs were identified in the homozygous state in individuals with both the classic and vortex patterns of dystrophic deposits, these common sequence variants do not appear to be associated with the determination of the affected phenotype in this family.…”

Section: Discussionmentioning

confidence: 96%

Vortex Pattern of Corneal Deposits in Granular Corneal Dystrophy Associated With the p.(Arg555Trp) Mutation in TGFBI

Kattan

Serna‐Ojeda

Sharma

et al. 2017

Cornea

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Purpose To describe two unrelated families with multiple members demonstrating a less commonly recognized vortex pattern of corneal deposits confirmed to be granular corneal dystrophy type 1(GCD1) following identification of the p.(Arg555Trp) mutation in the transforming growth factor β-induced gene (TGFBI). Methods A slit lamp examination was performed on individuals from two families, one of Mexican descent and a second of Italian descent. Following DNA extraction from affected individuals and their unaffected relatives, TGFBI screening was performed. Results Eight of 20 individuals in the Mexican family and 20 of 55 in the Italian family demonstrated corneal stromal opacities. Seven of the eight affected individuals in the Mexican family and four of the 20 affected individuals in the Italian family demonstrated a phenotype characterized by a “sea fan” or vortex pattern of superficial stromal corneal deposits originating from the inferior aspect of the cornea. Screening of TGFBI in both families revealed a heterozygous missense mutation (p.(Arg555Trp)) in exon 12, confirming the diagnosis of GCD1. Conclusion Our findings demonstrate that GCD1 may present with a vortex pattern of anterior stromal deposits. Although this pattern of dystrophic deposits is not recognized by clinicians as a typical phenotype of GCD1, it is consistent with the production of the majority of the TGFBI protein by the corneal epithelium.

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Section: Discussionmentioning

confidence: 96%

Vortex Pattern of Corneal Deposits in Granular Corneal Dystrophy Associated With the p.(Arg555Trp) Mutation in TGFBI

Kattan

Serna‐Ojeda

Sharma

et al. 2017

Cornea

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“…Genetics : A great majority of subjects with GCD1 have a C to T transition at nucleotide position 1663 of TGFBI exon 12, predicting a p.Arg555Trp change of the protein in heterozygous patients. However, the typical GCD1 phenotype has also been associated with three other variants: G to A transition at position 337 causing p.Val113Ile substitution in a Spanish and Mexican family (Ann et al, ; Zenteno et al, ), C to A transversion at nucleotide 370 causing a p.Arg124Ser substitution in Asian families (H. S. Stewart et al, ), and a C to G transversion at nucleotide 1548 causing a p.Ser516Arg substitution in an Indian family (Paliwal et al, ). In the juvenile‐confluent form, a defect at p.Arg124His was found to be responsible for the disease in five Japanese homozygous families (Mashima et al, ).…”

Section: Involvement In Disease: Clinical and Diagnostic Relevancementioning

confidence: 99%

Mutation update:TGFBIpathogenic and likely pathogenic variants in corneal dystrophies

et al. 2019

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Human transforming growth factor β‐induced (TGFBI), is a gene responsible for various corneal dystrophies. TGFBI produces a protein called TGFBI, which is involved in cell adhesion and serves as a recognition sequence for integrins. An alteration in cell surface interactions could be the underlying cause for the progressive accumulation of extracellular deposits in different layers of the cornea with the resulting changes of refractive index and transparency. To this date, 69 different pathogenic or likely pathogenic variants in TGFBI have been identified in a heterozygous or homozygous state in various corneal dystrophies, including a novel variant reported here. All disease‐associated variants were inherited as autosomal‐dominant traits but one; this latter was inherited as an autosomal recessive trait. Most corneal dystrophy‐associated variants are located at amino acids Arg124 and Arg555. To keep the list of corneal dystrophy‐associated variant current, we generated a locus‐specific database for TGFBI (http://databases.lovd.nl/shared/variants/TGFBI) containing all pathogenic and likely pathogenic variants reported so far. Non‐disease‐associated variants are described in specific databases, like gnomAD and ExAC but are not listed here. This article presents the most recent up‐to‐date list of disease‐associated variants.

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“…To date, only three previous reports have investigated the role of TGFBI variants in CDs in South European patients from Spain . Herein, we extend our previous study to characterize the genetic alterations underlying atypical CD in a singular cohort characterized by late disease onset, the absence of the recurrent erosion syndrome and bilateral round deposits in deep and mid corneal stroma that seems to evolve forming branched filamentous opacities gradually.…”

Section: Introductionmentioning

confidence: 60%

“…Herein we report the clinical characterization of, to the best of our knowledge, the largest CD cohort carrying the TGFBI p.(L558P) variant, which can be considered representative of the South European population. This sequence variant has previously been found only in patients from two apparently unrelated Ukrainian families and in three cases from a unique Spanish family . Therefore, the high prevalence of this variant among the studied Spanish families may indicate the existence of a founder effect, although a detailed analysis of genetic markers is required to confirm this hypothesis.…”

Section: Discussionmentioning

confidence: 85%

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

Campos-Mollo

Varela-Conde

Arriola‐Villalobos

et al. 2019

Clinical Exper Ophthalmology

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Importance Rare transforming growth factor beta‐induced (TGFBI) gene variants are involved in autosomal dominant corneal dystrophies (CDs) with heterogeneous clinical features. 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 Retrospective cohort study (from May 2014 to September 2017). Participants Thirty‐five individuals from 10 unrelated South European families presenting atypical lattice CD (LCD) were included. 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 p.(L558P) variant of TGFBI gene. 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 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.

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Variant lattice corneal dystrophy associated with compound heterozygous mutations in theTGFBIgene

Cited by 11 publications

References 17 publications

Vortex Pattern of Corneal Deposits in Granular Corneal Dystrophy Associated With the p.(Arg555Trp) Mutation in TGFBI

Vortex Pattern of Corneal Deposits in Granular Corneal Dystrophy Associated With the p.(Arg555Trp) Mutation in TGFBI

Mutation update:TGFBIpathogenic and likely pathogenic variants in corneal dystrophies

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

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