title: Four mutations (three novel, one founder) in TACSTD2 among Iranian GDLD patients.
abstract: OBJECTIVE
  To perform a mutation screening of TACSTD2 in 13 Iranian Gelatinous Drop-like Corneal Dystrophy (GDLD) pedigrees. To assess genotype-phenotype correlations. To determine intragenic SNP haplotypes associated with the mutations, so as to gain information on their origin.
  
  
  METHODS
  The coding region of TACSTD2 was sequenced in the probands of 13 unrelated Iranian GDLD pedigrees. Variations were assessed in other available affected and unaffected family members and in unrelated normal control subjects by restriction fragment length polymorphism (RFLP). The variations were classified as being associated with disease if they segregated with the disease phenotype in the families, were not observed in 100 control individuals, disrupted protein expression, or affected conserved positions in the coded protein. Three intragenic single-nucleotide polymorphisms (SNPs) were used to define haplotypes associated with putative disease-causing mutations.
  
  
  RESULTS
  The probands were each homozygous for one of four putative disease-causing variations observed in TACSTD2: C66X, F114C, L186P, and E227K. Three of these are novel. E227K was found in 10 of the Iranian patients. There were some phenotypic differences among different patients carrying this mutation-for example, with respect to age at onset. Genotyping of intragenic SNPs identified four haplotypes. C66X, F114C, and L186P were each associated with a haplotype common among control chromosomes, whereas all E227K alleles were associated with a haplotype not found among the control chromosomes.
  
  
  CONCLUSIONS
  Although mutations in TACSTD2 among Iranian patients with GDLD were heterogeneous, E227K was found to be a common mutation. It is suggested that E227K may be a founder mutation in this population. Based on positions of known mutations in TACSTD2, significance of the thyroglobulin domain of the TACSTD2 protein in the pathogenesis of GDLD is suggested.
authors: National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
authors: Afagh
authors: A
authors: Alavi
authors: Elahe
authors: E
authors: Elahi
authors: Mehdi Hosseini
authors: MH
authors: Tehrani
authors: Fahimeh Asadi
authors: FA
authors: Amoli
authors: Mohammad-Ali
authors: MA
authors: Javadi
authors: Nasrin
authors: N
authors: Rafati
authors: Mohsen
authors: M
authors: Chiani
authors: Setareh Sadat
authors: SS
authors: Banihosseini
authors: Behnaz
authors: B
authors: Bayat
authors: Reza
authors: R
authors: Kalhor
authors: Seyed S H
authors: SS
authors: Amini
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000686:Amyloidosis / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002648:Child; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007492:Iran; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499380:TACSTD2 protein, human