title: [Molecular genetic and histopathological examinations for genotype-phenotype analysis in patients with TGFBI-linked corneal dystrophy].
abstract: OBJECTIVE
  Different missense mutations in the TGFBI gene cause granular (Groenouw CDGG1, Avellino CDA, Reis-Bücklers CDB1) and lattice (Type I; Biber-Haab-Dimmer; CDL1) corneal dystrophies and, in some reports, corneal dystrophy Thiel-Behnke (CDB2). We report on the mutation spectrum and the genotype-phenotype correlations on the basis of clinical and histopathological examinations of 13 German families with TGFBI-linked corneal dystrophies.
  
  
  METHODS
  In 31 patients with different corneal dystrophies, DNA was extracted from leukocytes of the peripheral blood and mutation analysis was performed by direct sequencing of the TGFBI gene. Clinical and histopathological findings were compared with the molecular genetic findings for genotype-phenotype correlations.
  
  
  RESULTS
  In 6 patients (2 families/one single person) with clinical and histopathological CDL1 we found a Missense mutation Arg124Cys and in 7 patients (3 families/one single person) with clinical and histopathological CDA we found a Missense mutation Arg124His in the exon 4 of the TGFBI gene. In 12 patients (4 families/2 single persons) with clinical and histopathological CDGG1 we found a Missense mutation Arg555Trypt in the codon 12 of the TGFBI gene. In all five patients (1 family/4 single persons) with clinical and histopathological CDB2 we could not find any mutation in the TGFBI gene. In one patient with exceptional clinical and histopathological findings we found a Missense mutation Ala546Asp, which was reported before only twice in connection with polymorphous corneal amyloidosis.
  
  
  CONCLUSIONS
  In comparison of our clinical and histopathological findings and the molecular genetic results we found a strong genotype-phenotype correlation in patients with TGFBI-linked corneal dystrophies. Rare mutations can lead to exceptional clinical and histopathological findings which cannot be classified into the different groups of corneal dystrophies. In our patients with CDB2 we could not find any molecular genetic correlation to the TGFBI gene.
authors.affiliation: Universitätsaugenklinik mit Poliklinik der Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Strasse 40, Halle. claudia.gruenauer-kloevekorn@medizin.uni-halle.de
authors.forename: C
authors.initials: C
authors.lastname: Grünauer-Kloevekorn
authors.forename: S
authors.initials: S
authors.lastname: Braeutigam
authors.forename: E
authors.initials: E
authors.lastname: Weidle
authors.forename: M
authors.initials: M
authors.lastname: Wolter-Roessler
authors.forename: F
authors.initials: F
authors.lastname: Tost
authors.forename: C
authors.initials: C
authors.lastname: Auw-Haedrich
authors.forename: H E
authors.initials: HE
authors.lastname: Völcker
authors.forename: W
authors.initials: W
authors.lastname: Heinritz
authors.forename: U
authors.initials: U
authors.lastname: Froster
authors.forename: G
authors.initials: G
authors.lastname: Duncker
mesh_terms: D000328:Adult; D003317:Corneal Dystrophies, Hereditary / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016212:Transforming Growth Factor beta / Q000235:genetics*; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D005819:Genetic Markers; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein