title: A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration.
abstract: BACKGROUND
  The GNAT1 gene encodes the α subunit of the rod transducin protein, a key element in the rod phototransduction cascade. Variants in GNAT1 have been implicated in stationary night-blindness in the past, but unlike other proteins in the same pathway, it has not previously been implicated in retinitis pigmentosa.
  
  
  METHODS
  A panel of 182 retinopathy-associated genes was sequenced to locate disease-causing mutations in patients with inherited retinopathies.
  
  
  RESULTS
  Sequencing revealed a novel homozygous truncating mutation in the GNAT1 gene in a patient with significant pigmentary disturbance and constriction of visual fields, a presentation consistent with retinitis pigmentosa. This is the first report of a patient homozygous for a complete loss-of-function GNAT1 mutation. The clinical data from this patient provide definitive evidence of retinitis pigmentosa with late onset in addition to the lifelong night-blindness that would be expected from a lack of transducin function.
  
  
  CONCLUSIONS
  These data suggest that some truncating GNAT1 variants can indeed cause a recessive, mild, late-onset retinal degeneration in human beings rather than just stationary night-blindness as reported previously, with notable similarities to the phenotype of the Gnat1 knockout mouse.
authors.affiliation: School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland.
authors.forename: Matthew
authors.initials: M
authors.lastname: Carrigan
authors.affiliation: Research Foundation, Royal Victoria Eye & Ear Hospital, Dublin, Ireland.
authors.forename: Emma
authors.identifier: http://orcid.org/0000-0002-3968-4855
authors.initials: E
authors.lastname: Duignan
authors.affiliation: School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland.
authors.forename: Pete
authors.initials: P
authors.lastname: Humphries
authors.affiliation: School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland.
authors.forename: Arpad
authors.initials: A
authors.lastname: Palfi
authors.affiliation: School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland Research Foundation, Royal Victoria Eye & Ear Hospital, Dublin, Ireland.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Kenna
authors.affiliation: School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland.
authors.forename: G Jane
authors.initials: GJ
authors.lastname: Farrar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D018389:Codon, Nonsense; D004247:DNA / Q000302:isolation & purification; D004596:Electroretinography; D015785:Eye Diseases, Hereditary / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009216:Myopia / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D009755:Night Blindness / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D012160:Retina / Q000503:physiopathology; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D035781:Siblings; D041623:Tomography, Optical Coherence; D015293:Transducin
chemical_list: D018389:Codon, Nonsense; D005136:Eye Proteins; C034809:GNAT1 protein, human; D004247:DNA; D020962:Heterotrimeric GTP-Binding Proteins; D015293:Transducin
keywords: Degeneration; Genetics; Retina