title: Lattice corneal dystrophy type IV (p.Leu527Arg) is caused by a founder mutation of the TGFBI gene in a single Japanese ancestor.
abstract: OBJECTIVE
  Lattice corneal dystrophy (LCD) type IV (LCD4) is a late-onset corneal dystrophy with amyloid deposition at the deep stromal layer of cornea. As with other corneal dystrophies, this LCD subtype is also caused by a mutation (p. Leu527Arg) of the transforming growth factor, beta-induced (TGFBI) gene. Although LCD type I has been reported worldwide, LCD4 has been reported only in the Japanese population. In the present study, a haplotype analysis was performed to investigate whether this LCD subtype is caused by a founder mutation.
  
  
  METHODS
  Genomic DNA samples were extracted from 13 unrelated patients with LCD4. As a control, genomic DNA samples from 96 normal volunteers were also analyzed. For the haplotype analysis, the samples were amplified by polymerase chain reaction (PCR), TA-cloned, isothermally amplified, and subjected to a 1-base primer extension assay against a mutation site (c.1580T>G) and six known single-nucleotide polymorphisms (SNPs; rs4669, rs2072239, rs7727725, rs17689879, rs6871571, and rs3792900), which are located adjacent to the mutation site.
  
  
  RESULTS
  The haplotype analysis revealed that all the disease-carrying alleles from the 13 LCD4 patients shared an identical haplotype, whereas non-disease-carrying alleles from the normal volunteers and the LCD4 patients exhibited four haplotypes. There was a statistically significant difference in the haplotype distribution between the disease-carrying and the non-disease-carrying alleles.
  
  
  CONCLUSIONS
  The findings of this study strongly indicate that LCD4 was caused by a founder mutation of the TGFBI gene that occurred in a single Japanese ancestor.
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Fukuoka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kawasaki
authors.forename: Kenta
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.forename: Akiko
authors.initials: A
authors.lastname: Fukumoto
authors.forename: Akira
authors.initials: A
authors.lastname: Murakami
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kinoshita
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D003317:Corneal Dystrophies, Hereditary / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D040362:Geographic Information Systems; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1