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



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.



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.



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.
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;
Nisha
N
Patel
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;
Mohammed A
MA
Aldahmesh
Department of Ophthalmology, College of Medicine, Al-Imam Muhammad Ibn Saud Islamic University, Riyadh, Saudi Arabia.|Department of Ophthalmology, Specialized Medical Centre Hospital, Riyadh, Saudi Arabia.
Hisham
H
Alkuraya
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;
Shamsa
S
Anazi
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;
Hadeel
H
Alsharif
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;|Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
Arif O
AO
Khan
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;
Asma
A
Sunker
Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Saleh
S
Al-Mohsen
Vitreo-retinal Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
Emad B
EB
Abboud
Vitreo-retinal Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
Sawsan R
SR
Nowilaty
Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Mohammed
M
Alowain
Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Hamad
H
Al-Zaidan
Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Bandar
B
Al-Saud
Department of Pediatrics, King Fahad Medical City, Riyadh, Saudi Arabia.
Ali
A
Alasmari
Department of Clinical Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
Ghada M H
GM
Abdel-Salam
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;|Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
Mohamed
M
Abouelhoda
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;
Firdous M
FM
Abdulwahab
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;
Niema
N
Ibrahim
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;|Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
Ewa
E
Naim
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;|Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
Banan
B
Al-Younes
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;|Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
Abeer
A
E AlMostafa
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;|Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
Abdulelah
A
AlIssa
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;
Mais
M
Hashem
Department of Structural Biology, College of Medicine, Yale University, New Haven, Connecticut, USA.
Olga
O
Buzovetsky
Department of Structural Biology, College of Medicine, Yale University, New Haven, Connecticut, USA.
Yong
Y
Xiong
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;|Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
Dorota
D
Monies
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;|Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
Nada
N
Altassan
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;
Ranad
R
Shaheen
Department of Ophthalmology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Selwa A F
SA
Al-Hazzaa
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;|Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
Fowzan S
0000-0003-4158-341X
FS
Alkuraya
D015820:Cadherins / Q000235:genetics*; D002268:Carboxypeptidases / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012160:Retina / Q000473:pathology; D058499:Retinal Dystrophies / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000073359:Exome Sequencing
C114483:CDH16 protein, human; D015820:Cadherins; C511724:DNAJC19 protein, human; D033681:Mitochondrial Membrane Transport Proteins; C000607347:AGBL5 protein, human; D002268:Carboxypeptidases