Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes
- Leen Abu-Safieh1,15,
- May Alrashed1,2,3,15,
- Shamsa Anazi1,
- Hisham Alkuraya1,4,
- Arif O. Khan5,
- Mohammed Al-Owain6,7,
- Jawahir Al-Zahrani1,
- Lama Al-Abdi1,
- Mais Hashem1,
- Salwa Al-Tarimi1,
- Mohammed-Adeeb Sebai1,
- Ahmed Shamia1,
- Mohamed D. Ray-zack1,
- Malik Nassan1,
- Zuhair N. Al-Hassnan6,7,
- Zuhair Rahbeeni6,
- Saad Waheeb8,9,
- Abdullah Alkharashi10,
- Emad Abboud11,
- Selwa A.F. Al-Hazzaa1,12,13 and
- Fowzan S. Alkuraya1,7,14,16
- 1Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia;
- 2UCL Institute of Ophthalmology, Department of Genetics, London EC1V 9EL, United Kingdom;
- 3Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11573, Saudi Arabia;
- 4Department of Ophthalmology, College of Medicine, Imam Muhammed Bin Saud Islamic University, Riyadh 13317, Saudi Arabia;
- 5Department of Pediatrics, King Khaled Eye Specialist Hospital, Riyadh 11462, Saudi Arabia;
- 6Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia;
- 7Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia;
- 8Department of Ophthalmology, King Faisal Specialist Hospital and Research Center, Jeddah 21499, Saudi Arabia;
- 9Department of Ophthalmology, College of Medicine, King Abdulaziz University, Jeddah 21352, Saudi Arabia;
- 10Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11573, Saudi Arabia;
- 11Department of Retina, King Khaled Eye Specialist Hospital, Riyadh 11462, Saudi Arabia;
- 12Department of Ophthalmology, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia;
- 13Department of Ophthalmology, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia;
- 14Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh 11573, Saudi Arabia
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↵15 These authors contributed equally to this work.
Abstract
Retinal dystrophy (RD) is a heterogeneous group of hereditary diseases caused by loss of photoreceptor function and contributes significantly to the etiology of blindness globally but especially in the industrialized world. The extreme locus and allelic heterogeneity of these disorders poses a major diagnostic challenge and often impedes the ability to provide a molecular diagnosis that can inform counseling and gene-specific treatment strategies. In a large cohort of nearly 150 RD families, we used genomic approaches in the form of autozygome-guided mutation analysis and exome sequencing to identify the likely causative genetic lesion in the majority of cases. Additionally, our study revealed six novel candidate disease genes (C21orf2, EMC1, KIAA1549, GPR125, ACBD5, and DTHD1), two of which (ACBD5 and DTHD1) were observed in the context of syndromic forms of RD that are described for the first time.
Footnotes
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↵16 Corresponding author
E-mail falkuraya{at}kfshrc.edu.sa
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.144105.112.
- Received June 3, 2012.
- Accepted October 4, 2012.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.
