Molecular diagnosis of putative Stargardt disease by capture next generation sequencing.
Stargardt Disease (STGD) is the commonest genetic form of juvenile or early adult onset macular degeneration, which is a genetically heterogeneous disease. Molecular diagnosis of STGD remains a challenge in a significant proportion of cases. To address this, seven patients from five putative STGD families were recruited. We performed capture next generation sequencing (CNGS) of the probands and searched for potentially disease-causing genetic variants in previously identified retinal or macular dystrophy genes. Seven disease-causing mutations in ABCA4 and two in PROM1 were identified by CNGS, which provides a confident genetic diagnosis in these five families. We also provided a genetic basis to explain the differences among putative STGD due to various mutations in different genes. Meanwhile, we show for the first time that compound heterozygous mutations in PROM1 gene could cause cone-rod dystrophy. Our findings support the enormous potential of CNGS in putative STGD molecular diagnosis.
School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
Xiao
X
Zhang
School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
Xianglian
X
Ge
Department of Ophthalmology, Beijing Children's Hospital, Capital Medical University, Beijing, China.
Wei
W
Shi
Department of Development and Planning, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Ping
P
Huang
Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Qingjie
Q
Min
School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
Minghan
M
Li
School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
Xinping
X
Yu
Department of Ophthalmology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Yaming
Y
Wu
Fuzhou Southeastern Eye Hospital, Fuzhou, China.
Guangyu
G
Zhao
Fuzhou Southeastern Eye Hospital, Fuzhou, China.
Yi
Y
Tong
School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
Zi-Bing
ZB
Jin
School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
Jia
J
Qu
School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
Feng
F
Gu
D000071916:AC133 Antigen; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics; D008297:Male; D025202:Molecular Diagnostic Techniques; D008969:Molecular Sequence Data; D010375:Pedigree; D010455:Peptides / Q000235:genetics*; D000080362:Stargardt Disease; D055815:Young Adult
C056475:ABCA4 protein, human; D000071916:AC133 Antigen; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides