title: A novel phenotype-genotype relationship with a TGFBI exon 14 mutation in a pedigree with a unique corneal dystrophy of Bowman's layer.
abstract: OBJECTIVE
  Corneal dystrophy of Bowman's layer (CDB) belongs to a group of dystrophies associated with mutations in the transforming growth factor-beta-induced (TGFBI) gene. CDB is further divided into a geographic variant (CDB1/Reis Bücklers, RBCD), and a honeycomb variant (CDB2/Thiel Behnke, TBCD). We undertook mutational analysis of TGFBI in a family with an unusual CDB variant and describe a novel phenotype-genotype association.
  
  
  METHODS
  Individuals from a pedigree with CDB underwent extensive phenotyping, including laser scanning in vivo confocal microscopy, and histological examination of four corneal buttons obtained at penetrating keratoplasty. Transmission electron microscopy of an excised allograft cornea from one affected individual was also performed. Following informed consent, DNA samples were collected. Polymerase chain reaction (PCR) and sequencing of all coding exons of TGFBI was performed. Family members were recruited with subsequent phenotyping and genotyping, and paternity testing.
  
  
  RESULTS
  Clinical examination and other phenotypic information confirmed a diagnosis of CDB, with various features either more suggestive of CDB1 or of CDB2. A mutation in exon 14, H626P, segregated with the disease in this pedigree. This mutation was confirmed with NlaIII restriction enzyme digest, and was not seen in 100 control chromosomes.
  
  
  CONCLUSIONS
  Within this pedigree, CDB segregates with an H626P mutation, which is previously described occurring in lattice corneal dystrophy. The majority of mutations in TGFBI previously described segregating with CDB1 and CDB2 are R124L and R555Q, respectively. Although a Bowman's layer dystrophy, the phenotype in this pedigree does not closely conform to the classical diagnostic criteria for either CDB1 or CDB2, and therefore represents a novel phenotype-genotype correlation.
authors: Department of Ophthalmology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors: Catherine E
authors: CE
authors: Wheeldon
authors: Betina H
authors: BH
authors: de Karolyi
authors: Dipika V
authors: DV
authors: Patel
authors: Trevor
authors: T
authors: Sherwin
authors: Charles N J
authors: CN
authors: McGhee
authors: Andrea L
authors: AL
authors: Vincent
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D001483:Base Sequence; D050541:Bowman Membrane / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003315:Cornea / Q000473:pathology / Q000648:ultrastructure; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology*; D016039:Corneal Transplantation; D005091:Exons / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014184:Transplantation, Homologous; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein