title: Variant lattice corneal dystrophy associated with compound heterozygous mutations in theTGFBIgene.
abstract: To report the clinical, histopathological and genetic features of a variant of lattice corneal dystrophy (LCD) associated with two pathogenic mutations in the transforming growth factor-B-induced (TGFBI) gene.
  
  
  
  Clinical characterisation was performed by slit lamp examination and in vivo confocal microscopic imaging (IVCM). Histopathological characterisation was performed with light microscopic examination of an excised corneal button and a peripheral blood samples were collected forTGFBIscreening.
  
  
  
  A 42-year-old woman presented with progressive photophobia and decreased visual acuity in both eyes. Slit lamp examination demonstrated punctate and linear branching opacities in the mid and posterior corneal stroma, corresponding to hyper-reflective opacities noted on IVCM and amyloid deposition noted on histopathological examination of an excised corneal button.TGFBIscreening revealed two previously reported heterozygous missense mutations: c.337G>A (p.(Val113Ile)) in exon 4 and c.1673T>C (p.(Leu558Pro)) in exon 12. Screening of an affected sibling with a similar phenotype revealed that she was also heterozygous for both mutations, while screening of another sibling with punctate but not linear stromal opacities revealed that she was heterozygous for only the p.(Leu558Pro) mutation.
  
  
  
  The p.(Val113Ile) mutation results in an alteration of the atypical LCD phenotype associated with the p.(Leu558Pro) mutation. This represents only the second report of the alteration of the phenotype of aTGFBIdystrophy by a second, non-homozygous pathogenic mutation, and thus provides insight into the phenotype-genotype correlation of theTGFBIdystrophies.
authors.affiliation: Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Lydia Bai-Tsin
authors.initials: LB
authors.lastname: Ann
authors.affiliation: Vissum, Instituto Oftalmológico de Alicante, Universidad Miguel Hernández, Alicante, Spain.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Abbouda
authors.affiliation: Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Ricardo F
authors.initials: RF
authors.lastname: Frausto
authors.affiliation: Vissum, Instituto Oftalmológico de Alicante, Universidad Miguel Hernández, Alicante, Spain.
authors.forename: Samira
authors.initials: S
authors.lastname: Huseynli
authors.affiliation: Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Kishan
authors.initials: K
authors.lastname: Gupta
authors.affiliation: Vissum, Instituto Oftalmológico de Alicante, Universidad Miguel Hernández, Alicante, Spain.|Division of Ophthalmology, Universidad Miguel Hernández, Alicante, Spain.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Alió
authors.affiliation: Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Aldave
mesh_terms: D000328:Adult; D003315:Cornea / Q000473:pathology*; D003317:Corneal Dystrophies, Hereditary / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D018613:Microscopy, Confocal; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020795:Photophobia / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*
keywords: Cornea; Dystrophy; Genetics