Tehran University of Medical Sciences Iranian Journal of Public Health 2251-6085 51 9 2022 09 04 2048 2059 EN Masroor Babar The University of Agriculture, Dera Ismail Khan, Pakistan Akhtar Ali Department of Biotechnology, Virtual University of Pakistan, Lahore, Pakistan Syed Abbas Department of Bioinformatics & Computational Biology, Virtual University of Pakistan, Lahore, Pakistan Mirza Hasnain Department of Bioinformatics & Computational Biology, Virtual University of Pakistan, Lahore, Pakistan Nida Babar Resident Histopathology, Shaukat Khanum Memorial Hospital, Lahore, Pakistan Hira Babar Resident Hematology, Mayo Hospital, Lahore, Pakistan Tanveer Hussain Department of Molecular Biology, Virtual University of Pakistan, Lahore, Pakistan Asif Nadeem Department of Molecular Biology, Virtual University of Pakistan, Lahore, Pakistan Namra Ayub Department of Biotechnology, Virtual University of Pakistan, Lahore, Pakistan Sundus Shahid Department of Biotechnology, Virtual University of Pakistan, Lahore, Pakistan Muhammad Pervez Department of Bioinformatics & Computational Biology, Virtual University of Pakistan, Lahore, Pakistan 2021 03 24 2021 07 18 Background: Retinitis pigmentosa (RP) belongs to pigmentary retinopathies, a generic name for all retinal dystrophies with a major phenotypical and genotypical variation, characterized by progressive reduction of photoreceptor functionality of the rod and cone. Global prevalence of RP is ~ 1/4000 and it can be inherited as autosomal dominant (adRP), autosomal recessive (arRP) or X- linked (xlRP). We designed this study to identify causative mutations in Pakistani families affected with arRP. Methods: In 2019, we recruited two unrelated Pakistani consanguineous families affected with progressive vision loss and night blindness from Punjab region. Clinical diagnosis confirmed the; bone spicule pigmentation of the retina, and an altered electroretinogram (EGR) response. Proband and healthy individual from each family were subjected for whole-exome sequencing (WES).  Various computational tools were used to analyze the Next Generation Sequencing (NGS) data and to predict the pathogenicity of the identified mutations. Results: WES data analysis highlighted two missense homozygous variants at position c.T1405A (p.S469T) in PLCE1 and c.T11C (p.V4A) in HPS1 genes in proband of both families. Healthy individuals of two families were tested negative for p.S469T and p.V4A mutations. The variant analysis study including molecular dynamic simulations predicted mutations as disease causing.  Conclusion: Compound effect of mutations in rarely linked PLCE1 and HPS1 genes could also cause RP. This study highlights the potential application of WES for a rapid and precise molecular diagnosis for heterogeneous genetic diseases such as RP. https://ijph.tums.ac.ir/index.php/ijph/article/view/24223 https://ijph.tums.ac.ir/index.php/ijph/article/download/24223/7718