title: A novel GUCY2D mutation in a Chinese family with dominant cone dystrophy.
abstract: OBJECTIVE
  To describe the clinical and genetic findings in a Chinese family with autosomal dominant cone dystrophy (adCOD).
  
  
  METHODS
  One family was examined clinically, and genomic DNA was extracted from venous blood of all participants. Genotyping and haplotyping analysis was performed on the known genetic loci for adCOD and autosomal dominant cone-rod dystrophies (adCORD) with a panel of polymorphic markers in this family. All coding exons of the AIPL1, PTTPNM3, and GUCY2D gene were directly sequenced. Allele-specific PCR was used to validate a substitution in all available family members and 100 normal controls. Bioinformatics analysis was done using the Garnier-Osguthorpe-Robson method to predict the effect of the variants detected on the secondary structure of the GUCY2D protein.
  
  
  RESULTS
  Clinical examination and pedigree analysis revealed a three-generation family with four members diagnosed with adCOD. Through genotyping, the disease-causing genes were mapped to chromosomes 17p13.1-2 (AIPL1, PITPNM3, and GUCY2D gene). A novel A->G transition at position 2545 (p.T849A) of the cDNA sequence was identified in the GUCY2D gene. No mutation was detected in the AIPL1 and PITPNM3 genes. This missense mutation co-segregated with the disease phenotype of the family but was not found in the 100 normal controls.
  
  
  CONCLUSIONS
  A novel missense mutation of the GUCY2D gene was identified in this study. Our results further confirm that the dimerization zone of RetGC-1 is the mutational hot region for COD and CORD.
authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Yanfan
authors.initials: Y
authors.lastname: Ren
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.forename: Changxi
authors.initials: C
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Dong
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002681:China; D019295:Computational Biology; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005190:Family; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006162:Guanylate Cyclase / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: D011956:Receptors, Cell Surface; C110715:guanylate cyclase 1; D006162:Guanylate Cyclase