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Genet Med. 2016 Jun;18(6):554-62. doi: 10.1038/gim.2015.127. Epub 2015 Sep 10.

Expanding the clinical, allelic, and locus heterogeneity of retinal dystrophies.

Author information

1
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;
2
Department of Ophthalmology, College of Medicine, Al-Imam Muhammad Ibn Saud Islamic University, Riyadh, Saudi Arabia.
3
Department of Ophthalmology, Specialized Medical Centre Hospital, Riyadh, Saudi Arabia.
4
Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
5
Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
6
Vitreo-retinal Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
7
Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
8
Department of Pediatrics, King Fahad Medical City, Riyadh, Saudi Arabia.
9
Department of Clinical Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
10
Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
11
Department of Structural Biology, College of Medicine, Yale University, New Haven, Connecticut, USA.
12
Department of Ophthalmology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
13
Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.

Abstract

PURPOSE:

Retinal dystrophies (RD) are heterogeneous hereditary disorders of the retina that are usually progressive in nature. The aim of this study was to clinically and molecularly characterize a large cohort of RD patients.

METHODS:

We have developed a next-generation sequencing assay that allows known RD genes to be sequenced simultaneously. We also performed mapping studies and exome sequencing on familial and on syndromic RD patients who tested negative on the panel.

RESULTS:

Our panel identified the likely causal mutation in >60% of the 292 RD families tested. Mapping studies on all 162 familial RD patients who tested negative on the panel identified two novel disease loci on Chr2:25,550,180-28,794,007 and Chr16:59,225,000-72,511,000. Whole-exome sequencing revealed the likely candidate as AGBL5 and CDH16, respectively. We also performed exome sequencing on negative syndromic RD cases and identified a novel homozygous truncating mutation in GNS in a family with the novel combination of mucopolysaccharidosis and RD. Moreover, we identified a homozygous truncating mutation in DNAJC17 in a family with an apparently novel syndrome of retinitis pigmentosa and hypogammaglobulinemia.

CONCLUSION:

Our study expands the clinical and allelic spectrum of known RD genes, and reveals AGBL5, CDH16, and DNAJC17 as novel disease candidates.Genet Med 18 6, 554-562.

PMID:
26355662
DOI:
10.1038/gim.2015.127
[Indexed for MEDLINE]

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