Exome sequencing as a tool of molecular screening of cataract affected families
Main Article Content
Keywords
Cataract, Linkage Analysis, Sanger Sequencing, Exome Sequencing
Abstract
Cataract is the opacity of eye lens which is amongst the major causes of blindness in all age groups around the world. This study involved genetic screening of 24 cataract affected families from Punjab and Balochistan provinces of Pakistan. The screening included linkage analysis for most prevalent cataract genes and two of these families, found linked, were subjected to Sanger sequencing for mutational analysis. Linkage to HSF4 and FYCO1 genes were indicated in two families but no significant mutation could be ascertained upon sequencing HSF4 gene. Three of the unlinked families including a positive control family were submitted to exome sequencing in search for novel mutations. Exome sequencing successfully re-identified an already known mutation (c.233G>A) in the positive control family and revealed potential variants in other families. This mutation was previously identified by using linkage analysis and re-identified in our study by exome sequencing. Indication of linkage in family CCHUS-27 may suggest that FYCO1 is the most prevalent cataract gene in Pakistan. The identification of known mutation in positive control family strengthens the reliability of exome sequencing for identification of mutations causing cataract.
References
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Riazuddin, S. Amer, Afshan Yasmeen, Qingjiong Zhang, Wenliang Yao, Muhammad Farooq Sabar, Zahoor Ahmed, Sheikh Riazuddin, and J. Fielding Hejtmancik. 2005. ‘A New Locus for Autosomal Recessive Nuclear Cataract Mapped to Chromosome 19q13 in a Pakistani Family’. Investigative Opthalmology & Visual Science 46 (2): 623. https://doi.org/10.1167/iovs.04-0955.
Sajjad, Naheed, Ingrid Goebel, Naseebullah Kakar, Abdul Majeed Cheema, Christian Kubisch, and Jamil Ahmad. 2008. ‘A Novel HSF4gene Mutation (p.R405X) Causing Autosomal Recessive Congenital Cataracts in a Large Consanguineous Family from Pakistan’. BMC Medical Genetics 9 (1): 99. https://doi.org/10.1186/1471-2350-9-99.
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Yasmeen, Afshan, S. Amer Riazuddin, Haiba Kaul, Sadia Mohsin, Mohsin Khan, Zaheeruddin A. Qazi, Idrees A. Nasir, et al. 2010. ‘Autosomal Recessive Congenital Cataract in Consanguineous Pakistani Families Is Associated with Mutations in GALK1’. Molecular Vision 16 (April): 682–88.
Anjum, Iram, Hans Eiberg, Shahid Mahmood Baig, Niels Tommerup, and Lars Hansen. 2010. ‘A Mutation in the FOXE3 Gene Causes Congenital Primary Aphakia in an Autosomal Recessive Consanguineous Pakistani Family’. Molecular Vision 16 (March): 549–55.
Ansar, Muhammad, Hyung-lok Chung, Rachel L. Taylor, Aamir Nazir, Samina Imtiaz, Muhammad T. Sarwar, Alkistis Manousopoulou, et al. 2018. ‘Bi-Allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts’. The American Journal of Human Genetics 103 (4): 568–78. https://doi.org/10.1016/j.ajhg.2018.09.004.
Bhinder, Munir Ahmad, Haleema Sadia, Nasir Mahmood, Muhammad Qasim, Zawar Hussain, Muhammad Mudassar Rashid, Muhammad Yasir Zahoor, et al. 2019. ‘Consanguinity: A Blessing or Menace at Population Level?’ Annals of Human Genetics 83 (4): 214–19. https://doi.org/10.1111/ahg.12308.
Borck, Guntram, Naseebullah Kakar, Jochen Hoch, Katrin Friedrich, Jan Freudenberg, Gudrun Nürnberg, Rüstem Yilmaz, et al. 2012. ‘An Alu Repeat-Mediated Genomic GCNT2 Deletion Underlies Congenital Cataracts and Adult i Blood Group’. Human Genetics 131 (2): 209–16. https://doi.org/10.1007/s00439-011-1062-1.
Chen, Jianjun, Zhiwei Ma, Xiaodong Jiao, Robert Fariss, Wanda Lee Kantorow, Marc Kantorow, Eran Pras, et al. 2011. ‘Mutations in FYCO1 Cause Autosomal-Recessive Congenital Cataracts’. The American Journal of Human Genetics 88 (6): 827–38. https://doi.org/10.1016/j.ajhg.2011.05.008.
Chen, Jianjun, Qiwei Wang, Patricia E. Cabrera, Zilin Zhong, Wenmin Sun, Xiaodong Jiao, Yabin Chen, et al. 2017. ‘Molecular Genetic Analysis of Pakistani Families with Autosomal Recessive Congenital Cataracts by Homozygosity Screening’. Investigative Opthalmology & Visual Science 58 (4): 2207. https://doi.org/10.1167/iovs.17-21469.
Forshew, Tim, Colin A. Johnson, Shagufta Khaliq, Shanaz Pasha, Catherine Willis, Rashida Abbasi, Louise Tee, et al. 2005. ‘Locus Heterogeneity in Autosomal Recessive Congenital Cataracts: Linkage to 9q and Germline HSF4 Mutations’. Human Genetics 117 (5): 452–59. https://doi.org/10.1007/s00439-005-1309-9.
Happ, Hannah, Eric Weh, Deborah Costakos, Linda M. Reis, and Elena V. Semina. 2016. ‘Case Report of Homozygous Deletion Involving the First Coding Exons of GCNT2 Isoforms A and B and Part of the Upstream Region of TFAP2A in Congenital Cataract’. BMC Medical Genetics 17 (1): 64. https://doi.org/10.1186/s12881-016-0316-0.
Hassan, Bilal, Ramsha Ahmed, Bo Li, Ayesha Noor, and Zahid ul Hassan. 2019. ‘A Comprehensive Study Capturing Vision Loss Burden in Pakistan (1990-2025): Findings from the Global Burden of Disease (GBD) 2017 Study’. PLoS ONE 14 (5): e0216492. https://doi.org/10.1371/journal.pone.0216492.
Irum, Bushra, Firoz Kabir, Nadav Shoshany, Shahid Y. Khan, Bushra Rauf, Muhammad Asif Naeem, Tanveer A. Qaiser, Sheikh Riazuddin, J. Fielding Hejtmancik, and S. Amer Riazuddin. 2022. ‘A Genomic Deletion Encompassing CRYBB2-CRYBB2P1 Is Responsible for Autosomal Recessive Congenital Cataracts’. Human Genome Variation 9 (1): 1–3. https://doi.org/10.1038/s41439-022-00208-7.
Irum, Bushra, Shahid Y. Khan, Muhammad Ali, Muhammad Daud, Firoz Kabir, Bushra Rauf, Fareeha Fatima, et al. 2016. ‘Deletion at the GCNT2 Locus Causes Autosomal Recessive Congenital Cataracts’. Edited by Usha P. Andley. PLOS ONE 11 (12): e0167562. https://doi.org/10.1371/journal.pone.0167562.
Irum, Bushra, Shahid Y. Khan, Muhammad Ali, Haiba Kaul, Firoz Kabir, Bushra Rauf, Fareeha Fatima, et al. 2016. ‘Mutation in LIM2 Is Responsible for Autosomal Recessive Congenital Cataracts’. Edited by Yong-Bin Yan. PLOS ONE 11 (11): e0162620. https://doi.org/10.1371/journal.pone.0162620.
Iseri, Sibel Ugur, Robert J. Osborne, Martin Farrall, Alexander William Wyatt, Ghazala Mirza, Gudrun Nürnberg, Christian Kluck, et al. 2009. ‘Seeing Clearly: The Dominant and Recessive Nature of FOXE3 in Eye Developmental Anomalies’. Human Mutation 30 (10): 1378–86. https://doi.org/10.1002/humu.21079.
Jiaox, Xiaodong, Shahid Y. Khan, Bushra Irum, Arif O. Khan, Qiwei Wang, Firoz Kabir, Asma A. Khan, et al. 2015. ‘Missense Mutations in CRYAB Are Liable for Recessive Congenital Cataracts’. Edited by Yong-Bin Yan. PLOS ONE 10 (9): e0137973. https://doi.org/10.1371/journal.pone.0137973.
Kaul, Haiba, S Amer Riazuddin, Mariam Shahid, Samra Kousar, Nadeem H Butt, Ahmad U Zafar, Shaheen N Khan, et al. 2010. ‘Autosomal Recessive Congenital Cataract Linked to EPHA2 in a Consanguineous Pakistani Family’. Molecular Vision.
Riazuddin, S. Amer, Laleh Amiri-Kordestani, Haiba Kaul, Tariq Butt, Xiaodong Jiao, Sheikh Riazuddin, and J. Fielding Hejtmancik. 2009. ‘Novel SIL1 Mutations in Consanguineous Pakistani Families Mapping to Chromosomes 5q31’. Molecular Vision 15 (May): 1050–56.
Riazuddin, S. Amer, Afshan Yasmeen, Qingjiong Zhang, Wenliang Yao, Muhammad Farooq Sabar, Zahoor Ahmed, Sheikh Riazuddin, and J. Fielding Hejtmancik. 2005. ‘A New Locus for Autosomal Recessive Nuclear Cataract Mapped to Chromosome 19q13 in a Pakistani Family’. Investigative Opthalmology & Visual Science 46 (2): 623. https://doi.org/10.1167/iovs.04-0955.
Sajjad, Naheed, Ingrid Goebel, Naseebullah Kakar, Abdul Majeed Cheema, Christian Kubisch, and Jamil Ahmad. 2008. ‘A Novel HSF4gene Mutation (p.R405X) Causing Autosomal Recessive Congenital Cataracts in a Large Consanguineous Family from Pakistan’. BMC Medical Genetics 9 (1): 99. https://doi.org/10.1186/1471-2350-9-99.
Saleem, Rani Saira, Sorath Noorani Siddiqui, Saba Irshad, Naeem Mahmood Ashraf, Arslan Hamid, Muhammad Azmat Ullah Khan, Muhammad Imran Khan, and Shazia Micheal. 2022. ‘Targeted Gene Sequencing of FYCO1 Identified a Novel Mutation in a Pakistani Family for Autosomal Recessive Congenital Cataract’. Molecular Genetics & Genomic Medicine 10 (8): e1985. https://doi.org/10.1002/mgg3.1985.
Yasmeen, Afshan, S. Amer Riazuddin, Haiba Kaul, Sadia Mohsin, Mohsin Khan, Zaheeruddin A. Qazi, Idrees A. Nasir, et al. 2010. ‘Autosomal Recessive Congenital Cataract in Consanguineous Pakistani Families Is Associated with Mutations in GALK1’. Molecular Vision 16 (April): 682–88.
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Published
Mar 02, 2024
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Najeeb Ullah, Faiza Munir, Sana Iqbal, Muhammad Ilyas, Jahangir Khan Achakzai , Abdul Bari, Munir Ahmad Bhinder. (2024). Exome sequencing as a tool of molecular screening of cataract affected families. Journal of Population Therapeutics and Clinical Pharmacology, 31(2), 849-859. https://jptcp.com/index.php/jptcp/article/view/4780
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All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Najeeb Ullah, Faiza Munir, Sana Iqbal, Muhammad Ilyas, Jahangir Khan Achakzai , Abdul Bari, Munir Ahmad Bhinder. (2024). Exome sequencing as a tool of molecular screening of cataract affected families. Journal of Population Therapeutics and Clinical Pharmacology, 31(2), 849-859. https://jptcp.com/index.php/jptcp/article/view/4780