title: Five novel CNGB3 gene mutations in Polish patients with achromatopsia.
abstract: OBJECTIVE
  To identify the genetic basis of achromatopsia (ACHM) in four patients from four unrelated Polish families.
  
  
  METHODS
  In this study, we investigated probands with a clinical diagnosis of ACHM. Ophthalmologic examinations, including visual acuity testing, color vision testing, and full-field electroretinography (ERG), were performed in all patients (with the exception of patient p4, who had no ERG). Direct DNA sequencing encompassing the entire coding region of the CNGB3 gene, eight exons of the GNAT2 gene, and exons 5-7 of the CNGA3 gene was performed. Segregation analysis for the presence and independent inheritance of two mutant alleles was performed in the three families available for study.
  
  
  RESULTS
  All patients showed typical achromatopsia signs and symptoms. Sequencing helped detect causative changes in the CNGB3 gene in all probands. Eight different mutations were detected in the CNGB3 gene, including five novel mutations: two splice site mutations (c.1579-1G>A and c.494-2A>T), one nonsense substitution (c.1194T>G), and two frame-shift mutations (c.393_394delGCinsTCCTGGTGA and c.1366delC). We also found three mutations: one splice site (c.1578+1G>A) and two frame-shift deletions that had been previously described (c.819_826del and c.1148delC). All respective parents were shown to be heterozygous carriers for the mutation detected in their children.
  
  
  CONCLUSIONS
  The present study reports five novel mutations in the CNGB3 gene, and thus broadens the spectrum of probably pathogenic mutations associated with ACHM. Together with molecular data, we provide a brief clinical description of the affected individuals.
authors.affiliation: Chair and Department of Medical Genetics, Poznan University of Medical Science, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wawrocka
authors.affiliation: Molecular Genetics Laboratory, Centre for Ophthalmology University Clinics Institute for Ophthalmic Research Tuebingen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kohl
authors.affiliation: Molecular Genetics Laboratory, Centre for Ophthalmology University Clinics Institute for Ophthalmic Research Tuebingen, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Baumann
authors.affiliation: Chair and Department of Medical Genetics, Poznan University of Medical Science, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Walczak-Sztulpa
authors.affiliation: Chair and Department of Medical Genetics, Poznan University of Medical Science, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wicher
authors.affiliation: Chair and Department of Medical Genetics, Poznan University of Medical Science, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Skorczyk-Werner
authors.affiliation: Chair and Department of Medical Genetics, Poznan University of Medical Science, Poland ; Center for Medical Genetics GENESIS, Poznan, Poland.
authors.forename: Maciej R
authors.initials: MR
authors.lastname: Krawczynski
mesh_terms: D000328:Adult; D001483:Base Sequence; D002648:Child; D018389:Codon, Nonsense; D003117:Color Vision Defects / Q000235:genetics* / Q000503:physiopathology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D011044:Poland; D022821:RNA Splice Sites; D017384:Sequence Deletion
chemical_list: C415904:CNGB3 protein, human; D018389:Codon, Nonsense; D054815:Cyclic Nucleotide-Gated Cation Channels; D022821:RNA Splice Sites