Mutation analysis of TGFBI and KRT12 in a case of concomitant keratoconus and granular corneal dystrophy

Graefes Arch Clin Exp Ophthalmol. 2017 Sep;255(9):1779-1786. doi: 10.1007/s00417-017-3699-5. Epub 2017 May 31.

Abstract

Purpose: This study is to summarize the concurrent keratoconus (KC) and granular corneal dystrophy (GCD) phenotype and identify the underlying genetic cause in a 23-year-old male patient.

Methods: A detailed family history and clinical data from the patient and his parents were collected by ophthalmologic examination. The candidate genes were captured and sequenced by targeted next-generation sequencing, and the results were confirmed by Sanger sequencing.

Results: The proband was clinically diagnosed as a case of concurrent KC and GCD, which is a very rare presentation. His father and grandmother were diagnosed as GCD in both eyes. There was no character of KC in his father's and grandmother's eyes. A heterozygous TGFBI mutation in exon 4 (c.370G > A) was identified in the proband, which was predicted to generate a missense mutation (p.R124H). The mutation also existed in his father and grandmother. A heterozygous KRT12 mutation in exon 8 (c.1456-1457ins GTA) was identified in the proband, which was predicted to generate an insert mutation and created a premature termination codon. The mutation did not exist in his father and grandmother. The two mutations did not exist in his mother and 200 unrelated normal controls.

Conclusions: KC can co-exist with GCD. The missense mutation (c.370G > A) in the TGFBI gene and insert mutation (c.1456-1457ins GAT) in the KRT12 gene were identified in a 23-year-old male patient with concurrent KC and GCD.

Keywords: Chinese; Granular corneal dystrophy; KRT12; Keratoconus; TGFBI.

MeSH terms

  • China
  • Corneal Dystrophies, Hereditary / complications
  • Corneal Dystrophies, Hereditary / genetics*
  • Corneal Dystrophies, Hereditary / metabolism
  • DNA / genetics*
  • DNA Mutational Analysis
  • Female
  • Heterozygote
  • Humans
  • Keratin-12 / genetics*
  • Keratin-12 / metabolism
  • Keratoconus / complications
  • Keratoconus / genetics*
  • Keratoconus / metabolism
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Pedigree
  • Polymerase Chain Reaction
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / metabolism
  • Young Adult

Substances

  • KRT12 protein, human
  • Keratin-12
  • Transforming Growth Factor beta
  • DNA