title: Variant phenotypes of incomplete achromatopsia in two cousins with GNAT2 gene mutations.
abstract: OBJECTIVE
  The present study was designed to elucidate the molecular genetic basis of a congenital stationary cone dysfunction characterized by congenital nystagmus, moderate visual impairment, and markedly disparate color vision deficiencies between two affected cousins.
  
  
  METHODS
  Ophthalmic examinations with emphasis on color vision and electrophysiology. Molecular genetic analysis of the X-linked cone opsin genes, mutation screening of the CNGA3, CNGB3, and GNAT2 genes, and heterologous splicing experiments.
  
  
  RESULTS
  Whereas the proband was found to carry a homozygous frameshift mutation (Tyr95fs) in GNAT2, her cousin was compound heterozygous for the Tyr95fs and a new intronic mutation c.461 + 24G-->A. Heterologous expression in COS7 cells showed that the latter causes a splicing defect that results in early translation termination. Yet, this mutation is leaky, giving rise to small amounts of correctly spliced transcripts and offer an explanation for the diverging clinical findings in the cousins, one best described as incomplete achromatopsia and the other with oligocone trichromacy.
  
  
  CONCLUSIONS
  The cases presented broaden the phenotypic spectrum of GNAT2 mutations and underline the increasing importance of molecular genetics in the clinical diagnosis of atypical ophthalmic phenotypes.
authors.affiliation: Gordon Norrie Centre for Genetic Eye Diseases, National Eye Clinic for the Visually Impaired, 1 Rymarksvej, DK-2900 Hellerup, Denmark. roseeye@visaid.dk
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosenberg
authors.forename: Britta
authors.initials: B
authors.lastname: Baumann
authors.forename: Susanne
authors.initials: S
authors.lastname: Kohl
authors.forename: Eberhart
authors.initials: E
authors.lastname: Zrenner
authors.forename: Arne Lund
authors.initials: AL
authors.lastname: Jorgensen
authors.forename: Bernd
authors.initials: B
authors.lastname: Wissinger
mesh_terms: D000293:Adolescent; D000328:Adult; D000409:Alanine; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D003118:Color Perception; D003117:Color Vision Defects / Q000235:genetics* / Q000503:physiopathology; D004274:DNA, Recombinant; D004596:Electroretinography; D005260:Female; D016368:Frameshift Mutation; D005998:Glycine; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D014443:Tyrosine
chemical_list: D004274:DNA, Recombinant; D014443:Tyrosine; D000409:Alanine; D005998:Glycine