title: Mutation analysis at codon 838 of the Guanylate Cyclase 2D gene in Spanish families with autosomal dominant cone, cone-rod, and macular dystrophies.
abstract: OBJECTIVE
  Heterozygous mutations around codon 838 of the guanylate cyclase 2D (GUCY2D) gene have recently been associated with more than a third of autosomal dominant macular dystrophy patients. The aim of our study was to evaluate the prevalence of these mutations in Spanish families with autosomal dominant cone, cone-rod, and macular dystrophies.
  
  
  METHODS
  Mutation analysis was performed by PCR amplification of exon 13 of GUCY2D and subsequent restriction analysis. To confirm the results, automatic sequencing analysis was also performed.
  
  
  RESULTS
  Among the 22 unrelated Spanish families included in the study, we found two associated disease mutations at codon 838 of the GUCY2D gene, one of which had not been previously described (p.R838P). This novel mutation exhibited phenotypic variability.
  
  
  CONCLUSIONS
  The prevalence of mutations around codon 838 of GUCY2D in our group of families (9.09%) is lower than that previously reported in other populations. However, the discovery of a novel mutation at codon 838 further suggests that this locus is a mutation hotspot within the GUCY2D gene, and confirms the importance of analyzing this codon to characterize molecularly these autosomal dominant retinal disorders.
authors.affiliation: Genetics Department, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz (IIS-FJD), Madrid, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Garcia-Hoyos
authors.forename: Carmen Laura
authors.initials: CL
authors.lastname: Auz-Alexandre
authors.forename: Berta
authors.initials: B
authors.lastname: Almoguera
authors.forename: Diego
authors.initials: D
authors.lastname: Cantalapiedra
authors.forename: Rosa
authors.initials: R
authors.lastname: Riveiro-Alvarez
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Lopez-Martinez
authors.forename: Ascension
authors.initials: A
authors.lastname: Gimenez
authors.forename: Fiona
authors.initials: F
authors.lastname: Blanco-Kelly
authors.forename: Almudena
authors.initials: A
authors.lastname: Avila-Fernandez
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Trujillo-Tiebas
authors.forename: Blanca
authors.initials: B
authors.lastname: Garcia-Sandoval
authors.forename: Carmen
authors.initials: C
authors.lastname: Ramos
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
mesh_terms: D003062:Codon; D004252:DNA Mutational Analysis; D005799:Genes, Dominant; D056726:Genetic Association Studies; D006162:Guanylate Cyclase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008268:Macular Degeneration / Q000453:epidemiology / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000473:pathology; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000473:pathology; D013030:Spain; D014792:Visual Acuity / Q000235:genetics; D044465:White People / Q000208:ethnology / Q000235:genetics*
chemical_list: D003062:Codon; D011956:Receptors, Cell Surface; C110715:guanylate cyclase 1; D006162:Guanylate Cyclase