June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Variant Lattice Corneal Dystrophy Associated with Compound Heterozygous Mutations in the TGFBI Gene
Author Affiliations & Notes
  • Anthony J Aldave
    UCLA, Los Angeles, CA
  • Lydia Ann
    UCLA, Los Angeles, CA
  • Alessandro Abbouda
    Vissum, Instituto Oftalmológico de Alicante, Alicante, Spain
  • Ricardo F Frausto
    UCLA, Los Angeles, CA
  • Kishan Gupta
    UCLA, Los Angeles, CA
  • Jorge Alio
    Vissum, Instituto Oftalmológico de Alicante, Alicante, Spain
  • Footnotes
    Commercial Relationships Anthony Aldave, None; Lydia Ann, None; Alessandro Abbouda, None; Ricardo Frausto, None; Kishan Gupta, None; Jorge Alio, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2519. doi:
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      Anthony J Aldave, Lydia Ann, Alessandro Abbouda, Ricardo F Frausto, Kishan Gupta, Jorge Alio; Variant Lattice Corneal Dystrophy Associated with Compound Heterozygous Mutations in the TGFBI Gene. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2519.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

To report the clinical, histopathologic, and genetic features of a variant of lattice corneal dystrophy (LCD) associated with two pathogenic mutations in the TGFBI gene.

 
Methods
 

Clinical characterization was performed by slit lamp examination and in vivo confocal microscopic imaging (IVCM). Histopathologic characterization was performed with light microscopic examination of an excised corneal button and a peripheral blood sample was collected for TGFBI screening.

 
Results
 

A 42-year-old woman complained of progressive photophobia and decreased visual acuity in both eyes. Slit lamp examination demonstrated linear and branching opacities in the mid and posterior corneal stroma, corresponding to hyperreflective opacities noted on IVCM and amyloid deposition noted on histopathologic examination of an excised corneal button. TGFBI screening revealed two previously reported heterozygous missense mutations: c.337G>A (p.(Val113Ile)) in exon 4 and c.1673T>C (p.(Leu558Pro)) in exon 12.

 
Conclusions
 

The p.(Leu558Pro) mutation results in an alteration of the granular corneal dystrophy phenotype associated with the p.(Val113Ile) mutation in an individual heterozygous for both, resulting in a variant form of lattice corneal dystrophy. This represents only the second report of the alteration of the phenotype of a TGFBI dystrophy by a second, non-homozygous pathogenic mutation, and thus provides insight into the phenotype-genotype correlation of the TGFBI dystrophies.  

 
Pedigree of family with a variant form of LCD. Filled symbols represent affected individuals; open symbols represent unaffected individuals; question mark (?) indicates individual of undetermined affected status; arrowhead indicates the proband; asterisks indicate individuals in whom TGFBI screening was performed. Chromatograms reveal the two TGFBI single nucleotide variants identified in individuals II-3 and II-4: c.337G>A (p.(Val113Ile)) and c.1673T>C (p.(Leu558Pro)).
 
Pedigree of family with a variant form of LCD. Filled symbols represent affected individuals; open symbols represent unaffected individuals; question mark (?) indicates individual of undetermined affected status; arrowhead indicates the proband; asterisks indicate individuals in whom TGFBI screening was performed. Chromatograms reveal the two TGFBI single nucleotide variants identified in individuals II-3 and II-4: c.337G>A (p.(Val113Ile)) and c.1673T>C (p.(Leu558Pro)).
 
 
Slit lamp photomicrograph of individual (Figure 1; II-4) with variant LCD. Discrete grey opacities are seen in the central posterior stroma while fine branching linear opacities are observed in the paracentral corneal stroma (arrows).
 
Slit lamp photomicrograph of individual (Figure 1; II-4) with variant LCD. Discrete grey opacities are seen in the central posterior stroma while fine branching linear opacities are observed in the paracentral corneal stroma (arrows).

 
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