Investigating the molecular basis of retinal degeneration in a familial cohort of pakistani decent by exome sequencing

Bruno Maranhao, Pooja Biswas, Alexander D.H. Gottsch, Mili Navani, Muhammad Asif Naeem, John Suk, Justin Chu, Sheen N. Khan, Rachel Poleman, Javed Akram, Sheikh Riazuddin, Pauline Lee, S. Amer Riazuddin, J. Fielding Hejtmancik, Radha Ayyagari

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22 Scopus citations


Purpose: To define the molecular basis of retinal degeneration in consanguineous Pakistani pedigrees with early onset retinal degeneration. Methods: A cohort of 277 individuals representing 26 pedigrees from the Punjab province of Pakistan was analyzed. Exomes were captured with commercial kits and sequenced on an Illumina HiSeq 2500. Candidate variants were identified using standard tools and analyzed using exomeSuite to detect all potentially pathogenic changes in genes implicated in retinal degeneration. Segregation analysis was performed by dideoxy sequencing and novel variants were additionally investigated for their presence in ethnicity-matched controls. Results: We identified a total of nine causal mutations, including six novel variants in RPE65, LCA5, USH2A, CNGB1, FAM161A, CERKL and GUCY2D as the underlying cause of inherited retinal degenerations in 13 of 26 pedigrees. In addition to the causal variants, a total of 200 variants each observed in five or more unrelated pedigrees investigated in this study that were absent from the dbSNP, HapMap, 1000 Genomes, NHLBI ESP6500, and ExAC databases were identified, suggesting that they are common in, and unique to the Pakistani population. Conclusions: We identified causal mutations associated with retinal degeneration in nearly half of the pedigrees investigated in this study through next generation whole exome sequencing. All novel variants detected in this study through exome sequencing have been cataloged providing a reference database of variants common in, and unique to the Pakistani population. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Original languageEnglish (US)
Article numbere0136561
JournalPloS one
Issue number9
StatePublished - Sep 9 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General


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