title: GNAT1 associated with autosomal recessive congenital stationary night blindness.
abstract: OBJECTIVE
  Congenital stationary night blindness is a nonprogressive retinal disorder manifesting as impaired night vision and is generally associated with other ocular symptoms, such as nystagmus, myopia, and strabismus. This study was conducted to further investigate the genetic basis of CSNB in a consanguineous Pakistani family.
  
  
  METHODS
  A consanguineous family with multiple individuals manifesting cardinal symptoms of congenital stationary night blindness was ascertained. All family members underwent detailed ophthalmic examination, including fundus photographic examination and electroretinography. Blood samples were collected and genomic DNA was extracted. Exclusion and genome-wide linkage analyses were completed and two-point LOD scores were calculated. Bidirectional sequencing of GNAT1 was completed, and quantitative expression of Gnat1 transcript levels were investigated in ocular tissues at different postnatal intervals.
  
  
  RESULTS
  The results of ophthalmic examinations were suggestive of early-onset stationary night blindness with no extraocular anomalies. The genome-wide scan localized the critical interval to chromosome 3, region p22.1-p14.3, with maximum two-point LOD scores of 3.09 at θ = 0, flanked by markers D3S3522 and D3S1289. Subsequently, a missense mutation in GNAT1, p.D129G, was identified, which segregated within the family, consistent with an autosomal recessive mode of inheritance, and was not present in 192 ethnically matched control chromosomes. Expression analysis suggested that Gnat1 is expressed at approximately postnatal day (P)7 and is predominantly expressed in the retina.
  
  
  CONCLUSIONS
  These data suggest that a homozygous missense mutation in GNAT1 is associated with autosomal recessive stationary night blindness.
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Muhammad Asif
authors.initials: MA
authors.lastname: Naeem
authors.forename: Venkata R M
authors.initials: VR
authors.lastname: Chavali
authors.forename: Shahbaz
authors.initials: S
authors.lastname: Ali
authors.forename: Muhammad
authors.initials: M
authors.lastname: Iqbal
authors.forename: Saima
authors.initials: S
authors.lastname: Riazuddin
authors.forename: Shaheen N
authors.initials: SN
authors.lastname: Khan
authors.forename: Tayyab
authors.initials: T
authors.lastname: Husnain
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sieving
authors.forename: Radha
authors.initials: R
authors.lastname: Ayyagari
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
authors.forename: J Fielding
authors.initials: JF
authors.lastname: Hejtmancik
authors.forename: S Amer
authors.initials: SA
authors.lastname: Riazuddin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004596:Electroretinography; D015785:Eye Diseases, Hereditary; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D040181:Genetic Diseases, X-Linked; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009216:Myopia / Q000175:diagnosis / Q000235:genetics*; D009755:Night Blindness / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D060888:Real-Time Polymerase Chain Reaction; D015293:Transducin
chemical_list: D005136:Eye Proteins; C034809:GNAT1 protein, human; D020962:Heterotrimeric GTP-Binding Proteins; D015293:Transducin