title: Novel decorin mutation in a Chinese family with congenital stromal corneal dystrophy.
abstract: OBJECTIVE
  The aim of this study was to characterize the congenital stromal corneal dystrophy (CSCD) pathological and clinical phenotype in a Chinese family with a novel mutation of decorin and its possible molecular pathogenesis.
  
  
  METHODS
  Molecular genetic analyses were performed on 5 patients with CSCD. Clinical characteristics, optical coherence tomography, and confocal microscopic study were evaluated. The corneal specimens from patients with CSCD were sent for light and electron microscopic evaluation. A protein modeling study was carried out to assess the effect of the mutation on the protein structure.
  
  
  RESULTS
  Sequencing analysis of DCN revealed that all patients with CSCD were heterozygous for a 1-bp deletion at nucleotide 962 (c.962delA) in exon 8. This causes a premature termination of the decorin protein by frameshift, causing the deletion of 33 amino acids in the C-terminal end of the decorin protein. Optical coherence tomography and confocal microscopic study demonstrated that the corneal lamellar structure was disrupted and that this is more severe in the anterior and posterior central stroma. Histopathological study showed that electron-lucent zones were present between the normal-appearing collagen lamellae in the patients with CSCD. Abnormally thinned collagen filaments were identified in the electron-lucent zones, which could be due to abnormal decorin binding to the collagen microfibrils. Protein modeling studies involving wild-type and mutant protein indicated that mutant decorin might be unable to bind to all 4 collagen microfibrils as the normal decorin would.
  
  
  CONCLUSIONS
  We present the clinical, histopathological, and molecular genetic assessment of a Chinese family with CSCD in which a novel DCN mutation was identified. Our findings add to the allelic heterogeneity of this rare form of inherited corneal disease.
authors.affiliation: *Department of Ophthalmology and Visual Sciences, Montefiore Medical Center, Albert Einstein School of Medicine, Bronx, NY; †New York Structural Genomics Research Consortium, Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY; ‡Henan Eye Institute, Zhengzhou, China; §Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD; ¶King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; and ‖Department of Ophthalmology, The First Teaching Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jing
authors.forename: P Rajesh
authors.initials: PR
authors.lastname: Kumar
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.forename: Deepak P
authors.initials: DP
authors.lastname: Edward
authors.forename: Siyu
authors.initials: S
authors.lastname: Tao
authors.forename: Liya
authors.initials: L
authors.lastname: Wang
authors.forename: Roy
authors.initials: R
authors.lastname: Chuck
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D002675:Child, Preschool; D003317:Corneal Dystrophies, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D004252:DNA Mutational Analysis; D058575:Decorin / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007223:Infant; D015948:Keratoplasty, Penetrating; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology
chemical_list: C546878:DCN protein, human; D058575:Decorin