title: Phenotypic characterization of a Chinese family with autosomal dominant cone-rod dystrophy related to GUCY2D.
abstract: BACKGROUND
  This study aimed to evaluate the clinical phenotype and investigate the molecular genetic defect in a Chinese family with autosomal dominant cone-rod dystrophy (ADCRD).
  
  
  METHODS
  Family history was collected and patients underwent regular ophthalmologic examinations. Two affected individuals underwent three-year follow-ups to analyze the course of the disease. Venous blood was collected from family members and genomic DNA was extracted. A whole genome linkage analysis of 11 family members was performed using an Illumina Infinium Human Linkage-12 panel. All exons and exon-intron boundaries of guanylate cyclase 2D gene (GUCY2D) were sequenced for familial gene mutation.
  
  
  RESULTS
  Decreased visual acuity and photophobia usually commenced in early childhood in these patients. The family demonstrated an age-dependent increase in macular abnormalities with progressive development of geographic atrophy. Electrophysiological testing revealed a marked loss of cone function. Initially, a genome-wide linkage analysis mapped the disease to chromosome 17 (1-36 cM), with a maximum LOD score of 1.505. Sequence analysis of the GUCY2D gene in the linkage interval detected a recurrent heterozygous mutation, c.2513G > C (p.R838P). This mutation appeared in all seven patients with ADCRD but did not appear in any of the four unaffected family members.
  
  
  CONCLUSIONS
  A missense mutation in the GUCY2D gene caused ADCRD in this family. Clinical follow-up of this family with a typical CRD phenotype revealed disease progression during the time period.
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Shuai Fu Yuan, Beijing 100730, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.forename: Fangtian
authors.initials: F
authors.lastname: Dong
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Ruxin
authors.initials: R
authors.lastname: Jiang
authors.forename: Ruifang
authors.initials: R
authors.lastname: Sui
mesh_terms: D000293:Adolescent; D000328:Adult; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004596:Electroretinography; D005260:Female; D005500:Follow-Up Studies; D006162:Guanylate Cyclase / Q000235:genetics* / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D012162:Retinal Degeneration / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D012374:Rod Cell Outer Segment / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D041623:Tomography, Optical Coherence; D014792:Visual Acuity; D055815:Young Adult
chemical_list: D011956:Receptors, Cell Surface; C110715:guanylate cyclase 1; D004247:DNA; D006162:Guanylate Cyclase