title: Mutations in GRM6 identified in consanguineous Pakistani families with congenital stationary night blindness.
abstract: OBJECTIVE
  This study was undertaken to investigate the causal mutations responsible for autosomal recessive congenital stationary night blindness (CSNB) in consanguineous Pakistani families.
  
  
  METHODS
  Two consanguineous families with multiple individuals manifesting symptoms of stationary night blindness were recruited. Affected individuals underwent a detailed ophthalmological examination, including fundus examination and electroretinography. Blood samples were collected and genomic DNA was extracted. Exclusion analyses were completed by genotyping closely spaced microsatellite markers, and two-point logarithm of odds (LOD) scores were calculated. All coding exons, along with the exon-intron boundaries of GRM6, were sequenced bidirectionally.
  
  
  RESULTS
  According to the medical history available to us, affected individuals in both families had experienced night blindness from the early years of their lives. Fundus photographs of affected individuals in both the families appeared normal, with no signs of attenuated arteries or bone spicule pigmentation. The scotopic electroretinogram (ERG) response were absent in all of the affected individuals, while the photopic measurements show reduced b-waves. During exclusion analyses, both families localized to a region on chromosome 5q that harbors GRM6, a gene previously associated with autosomal recessive CSNB. Bidirectional sequencing of GRM6 identified homozygous single base pair changes, specifically c.1336C>T (p.R446X) and c.2267G>A (p.G756D) in families PKRP170 and PKRP172, respectively.
  
  
  CONCLUSIONS
  We identified a novel nonsense and a previously reported missense mutation in GRM6 that were responsible for autosomal recessive CSNB in patients of Pakistani decent.
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.affiliation: The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore MD.
authors.forename: Alexander D H
authors.initials: AD
authors.lastname: Gottsch
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Inayat
authors.initials: I
authors.lastname: Ullah
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Shaheen N
authors.initials: SN
authors.lastname: Khan
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Tayyab
authors.initials: T
authors.lastname: Husnain
authors.affiliation: Allama Iqbal Medical College, University of Health Sciences, Lahore, Pakistan.
authors.forename: Nadeem H
authors.initials: NH
authors.lastname: Butt
authors.affiliation: Layton Rahmatulla Benevolent Trust Hospital, Lahore, Pakistan.
authors.forename: Zaheeruddin A
authors.initials: ZA
authors.lastname: Qazi
authors.affiliation: Allama Iqbal Medical College, University of Health Sciences, Lahore, Pakistan ; National Centre for Genetic Diseases, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan.
authors.forename: Javed
authors.initials: J
authors.lastname: Akram
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan ; Allama Iqbal Medical College, University of Health Sciences, Lahore, Pakistan ; National Centre for Genetic Diseases, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan.
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
authors.affiliation: Shiley Eye Institute, University of California San Diego, La Jolla CA.
authors.forename: Radha
authors.initials: R
authors.lastname: Ayyagari
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda MD.
authors.forename: J Fielding
authors.initials: JF
authors.lastname: Hejtmancik
authors.affiliation: The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore MD.
authors.forename: S Amer
authors.initials: SA
authors.lastname: Riazuddin
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002895:Chromosomes, Human, Pair 5; D003241:Consanguinity; D004596:Electroretinography; D005091:Exons; D015785:Eye Diseases, Hereditary / Q000235:genetics* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005808:Genes, Recessive; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000473:pathology; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009216:Myopia / Q000235:genetics* / Q000473:pathology; D009755:Night Blindness / Q000235:genetics* / Q000473:pathology; D010154:Pakistan; D010375:Pedigree; D017470:Receptors, Glutamate / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: C576075:GRM6 protein, human; D017470:Receptors, Glutamate