title: Novel CNGA3 and CNGB3 mutations in two Pakistani families with achromatopsia.
abstract: OBJECTIVE
  To identify the genetic defect in two Pakistani families with autosomal recessive achromatopsia.
  
  
  METHODS
  Two families (RP26 and RP44) were originally diagnosed with retinal dystrophy based upon their medical history. To localize the causative genes in these families, homozygosity mapping was performed using Affymetrix 10K single nucleotide polymorphism (SNP) arrays. Sequence analysis was used to find the mutations in candidate genes cyclic nucleotide-gated channel alpha-3 (CNGA3; family RP26) and cyclic nucleotide-gated channel beta-3 (CNGB3; family RP44). Control individuals were analyzed by allele-specific PCR for the CNGA3 mutation and BstXI restriction analysis for the CNGB3 mutation. After genetic analysis, clinical diagnosis was re-evaluated by electroretinography and color vision testing. During the course of this study, selected affected members of family RP26 were given pink glasses as supportive therapy.
  
  
  RESULTS
  Sequence analysis of the positional candidate genes identified a novel missense mutation in CNGA3 (c.822G>T; p.R274S) in family RP26, and a novel CNGB3 frameshift mutation (c.1825delG; p.V609WfsX9) in family RP44. Clinical re-evaluation after genetic analysis revealed that both families have segregating autosomal recessive achromatopsia.
  
  
  CONCLUSIONS
  Genetic analysis of two Pakistani families with retinal disease enabled the establishment of the correct diagnosis of achromatopsia. Two novel mutations were identified in CNGA3 and CNGB3 that are both specifically expressed in cone photoreceptors. Re-evaluation of the clinical status revealed that both families had achromatopsia. The use of pink glasses in patients was helpful in reducing photophobia and enabled rod-mediated vision.
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Chak Shahzad, Islamabad, Pakistan.
authors.forename: Maleeha
authors.initials: M
authors.lastname: Azam
authors.forename: Rob W J
authors.initials: RW
authors.lastname: Collin
authors.forename: Syed Tahir Abbas
authors.initials: ST
authors.lastname: Shah
authors.forename: Aftab Ali
authors.initials: AA
authors.lastname: Shah
authors.forename: Muhammad Imran
authors.initials: MI
authors.lastname: Khan
authors.forename: Alamdar
authors.initials: A
authors.lastname: Hussain
authors.forename: Ahmed
authors.initials: A
authors.lastname: Sadeque
authors.forename: Tim M
authors.initials: TM
authors.lastname: Strom
authors.forename: Alberta A H J
authors.initials: AA
authors.lastname: Thiadens
authors.forename: Susanne
authors.initials: S
authors.lastname: Roosing
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.forename: Raheel
authors.initials: R
authors.lastname: Qamar
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D003116:Color; D003117:Color Vision Defects / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics*; D004596:Electroretinography; D005139:Eyeglasses; D016368:Frameshift Mutation; D005654:Fundus Oculi; D015870:Gene Expression; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010154:Pakistan; D020795:Photophobia / Q000209:etiology / Q000503:physiopathology / Q000534:rehabilitation; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells; D014785:Vision, Ocular
chemical_list: C518238:CNGA3 protein, human; C415904:CNGB3 protein, human; D054815:Cyclic Nucleotide-Gated Cation Channels
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