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      https://www.ias.ac.in/article/fulltext/jgen/100/0057

    • Keywords

       

      Pakistani family; leber congenital amaurosis; GUCY2D gene; exome sequencing; genomewide scan.

    • Abstract

       

      Leber congenital amaurosis (LCA) is a rare form of early onset vision loss or blindness due to retinal dystrophy. This condition is characterized by early vision loss, nystagmus and severe retinal dysfunction. To date, genetic studies have reported 19 genes to be associated with autosomal recessive LCA, most of which are involved in the retinal morphology and the physiology of the phototransduction pathway. In the current study, a large consanguineous family segregating congenital blindness was ascertained from the Dera IsmailKhan region of Pakistan. Genetic analysis was performed through genomewide SNP genotyping (for homozygosity-by-descent mapping), whole-exome sequencing (for mutation identification) and Sanger sequencing (for segregation analysis). In silico structural predictions were performed through SWISS-Model (structure prediction) and ClusPro (molecular docking). Molecular investigation of the present LCA family identified a novel homozygous missense mutation p.Asp306Val in GUCY2D gene (NM_000180.3:c.917A>T). In silico structuralmodelling and interaction studies predicted significant changes in protein folding and interacting residues. The present molecular genetic study further extends the mutational spectrum of GUCY2D in LCA, and its genetic heterogeneity in the Pakistani population. The findings of the computational studies on protein structure and interaction profile predicted pathogenic consequences of p.Asp306Val on GUCY2D function.

    • Author Affiliations

       

      HADIA GUL1 ABDUL HALEEM SHAH1 RICARDO HARRIPAUL2 SUMRA WAJID ABBASI3 MUHAMMAD FAHEEM3 MUHAMMAD ZUBAIR4 5 MUHAMMAD MUZAMMAL4 SAADULLAH KHAN6 JOHN B. VINCENT2 7 MUZAMMIL AHMAD KHAN4

      1. Institute of Biological Sciences, Gomal University, D.I.Khan 29050, Khyber Pakhtunkhwa, Pakistan
      2. Molecular Neuropsychiatry and Development (MiND) Lab, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada
      3. Department of Biological Sciences, National University of Medical Sciences, Rawalpindi 46000, Punjab, Pakistan
      4. Gomal Centre of Biochemistry and Biotechnology, Gomal University, D.I.Khan 29050, Khyber Pakhtunkhwa, Pakistan
      5. Department of Cell and Developmental Biology, School of Life Sciences, University of Science and Technology, Hefei 230026, Anhui, People’s Republic of China
      6. Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology, Kohat 26060, Khyber Pakhtunkhwa, Pakistan
      7. Department of Psychiatry, University of Toronto, Toronto, ON M5S 1A1, Canada
    • Dates

       
  • Journal of Genetics | News

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