%0 Journal Article %J Retina %D 2019 %T PHENOTYPIC VARIABILITY OF RECESSIVE RDH12-ASSOCIATED RETINAL DYSTROPHY. %A Zou, Xuan %A Fu, Qing %A Fang, Sha %A Li, Hui %A Ge, Zhongqi %A Yang, Lizhu %A Xu, Mingchu %A Sun, Zixi %A Li, Huajin %A Yumei Li %A Dong, Fangtian %A Rui Chen %A Sui, Ruifang %K Adolescent %K Adult %K Alcohol Oxidoreductases %K Biological Variation, Population %K Child %K Child, Preschool %K DNA Mutational Analysis %K Electroretinography %K Eye Diseases, Hereditary %K Female %K Genotype %K Humans %K Male %K Middle Aged %K Mutation %K Pedigree %K Phenotype %K Retinal Dystrophies %K Visual Acuity %K Young Adult %X

PURPOSE: To characterize the phenotypic variability and report the genetic defects in a cohort of Chinese patients with biallelic variants of the retinol dehydrogenase 12 (RDH12) gene.

METHODS: The study included 38 patients from 38 unrelated families with biallelic pathogenic RDH12 variants. Systematic next-generation sequencing data analysis, Sanger sequencing validation, and segregation analysis were used to identify the pathogenic mutations. Detailed ophthalmic examinations, including electroretinogram, fundus photography, fundus autofluorescence and optical coherence tomography, and statistical analysis were performed to evaluate phenotype variability.

RESULTS: Twenty-five different mutations of RDH12 were identified in the 38 families. Six of these variants were novel. Val146Asp was observed at the highest frequency (23.7%), and it was followed by Arg62Ter (14.5%) and Thr49Met (9.2%). Twenty-three probands were diagnosed with early-onset severe retinal dystrophy, 6 with Leber congenital amaurosis, 7 with autosomal recessive retinitis pigmentosa, and 2 with cone-rod dystrophy. Self-reported nyctalopia occurred in about a half of patients (55.3%) and was significantly more common among older patients (P < 0.01). Nyctalopia was not significantly associated with best-corrected visual acuity (P = 0.72), but older patients had significantly greater best-corrected visual acuity loss (P < 0.01). Only 15.8% of the patients had nystagmus, which was significantly more likely to occur among 36.8% of the patients with hyperopia >3D (P < 0.01) and/or in cases of reduced best-corrected visual acuity (P = 0.01), but was not associated with age (P = 0.87).

CONCLUSION: Several high-frequency RDH12 variants were identified in patients with inherited retinal dystrophies, most of which were missense mutations. Variable but characteristic phenotypes of a progressive nature was observed. Overall, the findings indicated that biallelic RDH12 mutations are a common cause of early-onset retinal dystrophy and a rare cause of cone-rod dystrophy.

%B Retina %V 39 %P 2040-2052 %8 2019 Oct %G eng %N 10 %1 https://www.ncbi.nlm.nih.gov/pubmed/30134391?dopt=Abstract %R 10.1097/IAE.0000000000002242 %0 Journal Article %J Nat Commun %D 2018 %T Author Correction: A proteomic landscape of diffuse-type gastric cancer. %A Ge, Sai %A Xia, Xia %A Ding, Chen %A Zhen, Bei %A Zhou, Quan %A Feng, Jinwen %A Yuan, Jiajia %A Chen, Rui %A Li, Yumei %A Ge, Zhongqi %A Ji, Jiafu %A Zhang, Lianhai %A Wang, Jiayuan %A Li, Zhongwu %A Lai, Yumei %A Hu, Ying %A Li, Yanyan %A Li, Yilin %A Gao, Jing %A Chen, Lin %A Xu, Jianming %A Zhang, Chunchao %A Jung, Sung Yun %A Choi, Jong Min %A Jain, Antrix %A Liu, Mingwei %A Song, Lei %A Liu, Wanlin %A Guo, Gaigai %A Gong, Tongqing %A Huang, Yin %A Qiu, Yang %A Huang, Wenwen %A Shi, Tieliu %A Zhu, Weimin %A Wang, Yi %A He, Fuchu %A Shen, Lin %A Qin, Jun %X

The original version of this Article contained an error in the email address of the corresponding author Jun Qin. The correct email is jqin1965@126.com. The error has been corrected in the HTML and PDF versions of the Article.

%B Nat Commun %V 9 %P 1850 %8 2018 May 08 %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/29739932?dopt=Abstract %R 10.1038/s41467-018-04166-z %0 Journal Article %J Genome Biol %D 2018 %T GRIPT: a novel case-control analysis method for Mendelian disease gene discovery. %A Wang, Jun %A Zhao, Li %A Wang, Xia %A Chen, Yong %A Xu, Mingchu %A Soens, Zachry T %A Ge, Zhongqi %A Wang, Peter Ronghan %A Wang, Fei %A Rui Chen %K Case-Control Studies %K Computer Simulation %K Genetic Association Studies %K Genetic Diseases, Inborn %K Humans %K Inheritance Patterns %K Sensitivity and Specificity %X

Despite rapid progress of next-generation sequencing (NGS) technologies, the disease-causing genes underpinning about half of all Mendelian diseases remain elusive. One main challenge is the high genetic heterogeneity of Mendelian diseases in which similar phenotypes are caused by different genes and each gene only accounts for a small proportion of the patients. To overcome this gap, we developed a novel method, the Gene Ranking, Identification and Prediction Tool (GRIPT), for performing case-control analysis of NGS data. Analyses of simulated and real datasets show that GRIPT is well-powered for disease gene discovery, especially for diseases with high locus heterogeneity.

%B Genome Biol %V 19 %P 203 %8 2018 Nov 26 %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/30477545?dopt=Abstract %R 10.1186/s13059-018-1579-x %0 Journal Article %J Nat Commun %D 2018 %T A proteomic landscape of diffuse-type gastric cancer. %A Ge, Sai %A Xia, Xia %A Ding, Chen %A Zhen, Bei %A Zhou, Quan %A Feng, Jinwen %A Yuan, Jiajia %A Chen, Rui %A Li, Yumei %A Ge, Zhongqi %A Ji, Jiafu %A Zhang, Lianhai %A Wang, Jiayuan %A Li, Zhongwu %A Lai, Yumei %A Hu, Ying %A Li, Yanyan %A Li, Yilin %A Gao, Jing %A Chen, Lin %A Xu, Jianming %A Zhang, Chunchao %A Jung, Sung Yun %A Choi, Jong Min %A Jain, Antrix %A Liu, Mingwei %A Song, Lei %A Liu, Wanlin %A Guo, Gaigai %A Gong, Tongqing %A Huang, Yin %A Qiu, Yang %A Huang, Wenwen %A Shi, Tieliu %A Zhu, Weimin %A Wang, Yi %A He, Fuchu %A Shen, Lin %A Qin, Jun %K Chemoradiotherapy, Adjuvant %K Datasets as Topic %K DNA Mutational Analysis %K Down-Regulation %K Exome %K Follow-Up Studies %K Gastrectomy %K Genes, Neoplasm %K Humans %K Immunohistochemistry %K Mutation %K Neoadjuvant Therapy %K Neoplasm Proteins %K Neoplasm Staging %K Oligonucleotide Array Sequence Analysis %K Prognosis %K Proteomics %K Sequence Analysis, DNA %K Signal Transduction %K Stomach %K Stomach Neoplasms %K Survival Analysis %K Tandem Mass Spectrometry %K Up-Regulation %X

The diffuse-type gastric cancer (DGC) is a subtype of gastric cancer with the worst prognosis and few treatment options. Here we present a dataset from 84 DGC patients, composed of a proteome of 11,340 gene products and mutation information of 274 cancer driver genes covering paired tumor and nearby tissue. DGC can be classified into three subtypes (PX1-3) based on the altered proteome alone. PX1 and PX2 exhibit dysregulation in the cell cycle and PX2 features an additional EMT process; PX3 is enriched in immune response proteins, has the worst survival, and is insensitive to chemotherapy. Data analysis revealed four major vulnerabilities in DGC that may be targeted for treatment, and allowed the nomination of potential immunotherapy targets for DGC patients, particularly for those in PX3. This dataset provides a rich resource for information and knowledge mining toward altered signaling pathways in DGC and demonstrates the benefit of proteomic analysis in cancer molecular subtyping.

%B Nat Commun %V 9 %P 1012 %8 2018 Mar 08 %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/29520031?dopt=Abstract %R 10.1038/s41467-018-03121-2 %0 Journal Article %J Invest Ophthalmol Vis Sci %D 2017 %T IFT81 as a Candidate Gene for Nonsyndromic Retinal Degeneration. %A Dharmat, Rachayata %A Liu, Wei %A Ge, Zhongqi %A Sun, Zixi %A Yang, Lizhu %A Li, Yumei %A Wang, Keqing %A Thomas, Kandace %A Sui, Ruifang %A Chen, Rui %K Animals %K Cells, Cultured %K Codon, Nonsense %K Disease Models, Animal %K DNA %K DNA Mutational Analysis %K Female %K Humans %K Male %K Muscle Proteins %K Mutation %K Phenotype %K Retina %K Retinal Degeneration %K Zebrafish %X

PURPOSE: IFT81, a core component of the IFT-B complex, involved in the bidirectional transport of ciliary proteins, has been recently implicated in syndromic ciliopathies. However, none of the IFT-B core complex proteins have been associated with nonsyndromic retinal dystrophies. Given the importance of ciliary transport in photoreceptor function and structural maintenance, we sought to investigate the impact of IFT (intraflagellar transport) mutations in nonsyndromic retinopathies.

METHODS: Whole exome sequencing was performed on 50 cone-rod dystrophy (CRD) patients that were previously screened for mutations in known retinal disease genes. The impact of candidate mutation was studied using in vitro cell system and in vivo zebrafish assay to determine the pathogenicity of the variant.

RESULTS: Compound heterozygous mutations in IFT81, including one nonsense (c.1213C>T, p.R405*) and one missense variant (c.1841T>C, p.L614P), were identified in a nonsyndromic CRD proband. Extensive functional analyses of the missense variant in cell culture and zebrafish strongly suggests its pathogenic nature. Loss of IFT81 impairs ciliogenesis and, interestingly, the missense variant displayed significantly reduced rescue of ciliogenesis in the IFT81 knockdown in vitro system. Consistently, dramatic reduction of rescue efficiency of the ift81 mutant zebrafish embryo by mRNA with the missense variant was observed, further supporting its pathogenicity.

CONCLUSIONS: Consistent with the function of the IFT-B complex in the maintenance of photoreceptor cilium, we report a case of mutations in a core IFT-B protein, IFT81. This represents the first report of mutations in IFT81 as a candidate gene for nonsyndromic retinal dystrophy, hence expanding the phenotype spectrum of IFT-B components.

%B Invest Ophthalmol Vis Sci %V 58 %P 2483-2490 %8 2017 May 01 %G eng %N 5 %1 https://www.ncbi.nlm.nih.gov/pubmed/28460050?dopt=Abstract %R 10.1167/iovs.16-19133 %0 Journal Article %J Dev Biol %D 2016 %T Identification of novel direct targets of Drosophila Sine oculis and Eyes absent by integration of genome-wide data sets. %A Jin, Meng %A Aibar, Sara %A Ge, Zhongqi %A Chen, Rui %A Aerts, Stein %A Mardon, Graeme %K Amino Acid Motifs %K Amino Acid Sequence %K Animals %K Chromatin Immunoprecipitation %K Compound Eye, Arthropod %K Consensus Sequence %K Drosophila melanogaster %K Drosophila Proteins %K Eye Proteins %K Gene Expression Regulation, Developmental %K Gene Ontology %K Genetic Association Studies %K Genome-Wide Association Study %K Homeodomain Proteins %K Imaginal Discs %K Larva %K Pupa %K RNA, Messenger %K Transcription, Genetic %K Transcriptome %X

Drosophila eye development is a complex process that involves many transcription factors (TFs) and interactions with their cofactors and targets. The TF Sine oculis (So) and its cofactor Eyes absent (Eya) are highly conserved and are both necessary and sufficient for eye development. Despite their many important roles during development, the direct targets of So are still largely unknown. Therefore the So-dependent regulatory network governing eye determination and differentiation is poorly understood. In this study, we intersected gene expression profiles of so or eya mutant eye tissue prepared from three different developmental stages and identified 1731 differentially expressed genes across the Drosophila genome. A combination of co-expression analyses and motif discovery identified a set of twelve putative direct So targets, including three known and nine novel targets. We also used our previous So ChIP-seq data to assess motif predictions for So and identified a canonical So binding motif. Finally, we performed in vivo enhancer reporter assays to test predicted enhancers from six candidate target genes and find that at least one enhancer from each gene is expressed in the developing eye disc and that their expression patterns overlap with that of So. We furthermore confirmed that the expression level of predicted direct So targets, for which antibodies are available, are reduced in so or eya post-mitotic knockout eye discs. In summary, we expand the set of putative So targets and show for the first time that the combined use of expression profiling of so with its cofactor eya is an effective method to identify novel So targets. Moreover, since So is highly conserved throughout the metazoa, our results provide the basis for future functional studies in a wide variety of organisms.

%B Dev Biol %V 415 %P 157-167 %8 2016 Jul 01 %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/27178668?dopt=Abstract %R 10.1016/j.ydbio.2016.05.007 %0 Journal Article %J Genome Res %D 2016 %T Integrative subcellular proteomic analysis allows accurate prediction of human disease-causing genes. %A Zhao, Li %A Chen, Yiyun %A Bajaj, Amol Onkar %A Eblimit, Aiden %A Xu, Mingchu %A Soens, Zachry T %A Wang, Feng %A Ge, Zhongqi %A Jung, Sung Yun %A He, Feng %A Li, Yumei %A Wensel, Theodore G %A Qin, Jun %A Chen, Rui %K Animals %K Eye Proteins %K Gene Expression Profiling %K Humans %K Mice %K Photoreceptor Cells %K Proteomics %K Retinal Diseases %K Transcriptome %X

Proteomic profiling on subcellular fractions provides invaluable information regarding both protein abundance and subcellular localization. When integrated with other data sets, it can greatly enhance our ability to predict gene function genome-wide. In this study, we performed a comprehensive proteomic analysis on the light-sensing compartment of photoreceptors called the outer segment (OS). By comparing with the protein profile obtained from the retina tissue depleted of OS, an enrichment score for each protein is calculated to quantify protein subcellular localization, and 84% accuracy is achieved compared with experimental data. By integrating the protein OS enrichment score, the protein abundance, and the retina transcriptome, the probability of a gene playing an essential function in photoreceptor cells is derived with high specificity and sensitivity. As a result, a list of genes that will likely result in human retinal disease when mutated was identified and validated by previous literature and/or animal model studies. Therefore, this new methodology demonstrates the synergy of combining subcellular fractionation proteomics with other omics data sets and is generally applicable to other tissues and diseases.

%B Genome Res %V 26 %P 660-9 %8 2016 May %G eng %N 5 %1 https://www.ncbi.nlm.nih.gov/pubmed/26912414?dopt=Abstract %R 10.1101/gr.198911.115 %0 Journal Article %J JAMA Ophthalmol %D 2016 %T Molecular and Clinical Findings in Patients With Knobloch Syndrome. %A Hull, Sarah %A Arno, Gavin %A Ku, Cristy A %A Ge, Zhongqi %A Waseem, Naushin %A Chandra, Aman %A Webster, Andrew R %A Robson, Anthony G %A Michaelides, Michel %A Weleber, Richard G %A Davagnanam, Indran %A Rui Chen %A Holder, Graham E %A Pennesi, Mark E %A Moore, Anthony T %K Adolescent %K Adult %K Child %K Child, Preschool %K Collagen Type VIII %K Collagen Type XVIII %K DNA Mutational Analysis %K Electroretinography %K Encephalocele %K Exfoliation Syndrome %K Exons %K Female %K Glaucoma, Open-Angle %K Humans %K Magnetic Resonance Imaging %K Male %K Molecular Biology %K Mutation %K Myopia, Degenerative %K Pedigree %K Photoreceptor Cells, Vertebrate %K Polymerase Chain Reaction %K Retinal Degeneration %K Retinal Detachment %K Vision Disorders %K Young Adult %X

IMPORTANCE: Knobloch syndrome is a rare, recessively inherited disorder classically characterized by high myopia, retinal detachment, and occipital encephalocele, but it is now known to have an increasingly variable phenotype. There is a lack of reported electrophysiologic data, and some key clinical features have yet to be described.

OBJECTIVE: To expand on current clinical, electrophysiologic, and molecular genetic findings in Knobloch syndrome.

DESIGN, SETTING, AND PARTICIPANTS: Twelve patients from 7 families underwent full ophthalmic examination and retinal imaging. Further investigations included electroretinography and neuroradiologic imaging. Bidirectional Sanger sequencing of COL18A1 was performed with segregation on available relatives. The study was conducted from July 4, 2013, to October 5, 2015. Data analysis was performed from May 20, 2014, to November 3, 2015.

MAIN OUTCOMES AND MEASURES: Results of ophthalmic and neuroradiologic assessment and sequence analysis of COL18A1.

RESULTS: Of the 12 patients (6 males; mean age at last review, 16 years [range, 2-38 years]), all had high myopia in at least 1 eye and severely reduced vision. A sibling pair had unilateral high myopia in their right eyes and near emmetropia in their left eyes from infancy. Anterior segment abnormalities included absent iris crypts, iris transillumination, lens subluxation, and cataract. Two patients with iris transillumination had glaucoma. Fundus characteristics included abnormal collapsed vitreous, macular atrophy, and a tesselated fundus. Five patients had previous retinal detachment. Electroretinography revealed a cone-rod pattern of dysfunction in 8 patients, was severely reduced or undetectable in 2 patients, and demonstrated cone-rod dysfunction in 1 eye with undetectable responses in the other eye in 2 patients. Radiologic imaging demonstrated occipital encephalocele or meningocele in 3 patients, occipital skull defects in 4 patients, minor occipital changes in 2 patients, and no abnormalities in 2 patients. Cutaneous scalp changes were present in 5 patients. Systemic associations were identified in 8 patients, including learning difficulties, epilepsy, and congenital renal abnormalities. Biallelic mutations including 2 likely novel mutations in COL18A1, were identified in 6 families that were consistent with autosomal recessive inheritance with a single mutation identified in a family with 2 affected children.

CONCLUSIONS AND RELEVANCE: This report describes new features in patients with Knobloch syndrome, including pigment dispersion syndrome and glaucoma as well as cone-rod dysfunction on electroretinography. Two patients had normal neuroradiologic findings, emphasizing that some affected individuals have isolated ocular disease. Awareness of the ocular phenotype may aid early diagnosis, appropriate genetic counseling, and monitoring for potential complications.

%B JAMA Ophthalmol %V 134 %P 753-62 %8 2016 Jul 01 %G eng %N 7 %1 https://www.ncbi.nlm.nih.gov/pubmed/27259167?dopt=Abstract %R 10.1001/jamaophthalmol.2016.1073 %0 Journal Article %J Invest Ophthalmol Vis Sci %D 2015 %T ATF6 Is Mutated in Early Onset Photoreceptor Degeneration With Macular Involvement. %A Xu, Mingchu %A Gelowani, Violet %A Eblimit, Aiden %A Wang, Feng %A Young, Marielle P %A Sawyer, Briana L %A Zhao, Li %A Jenkins, Glen %A Creel, Donnell J %A Wang, Keqing %A Ge, Zhongqi %A Wang, Hui %A Li, Yumei %A Hartnett, M Elizabeth %A Chen, Rui %K Activating Transcription Factor 6 %K Age Factors %K Child, Preschool %K Female %K Humans %K Macula Lutea %K Mutation %K Photoreceptor Cells, Vertebrate %K Retinal Diseases %X

PURPOSE: Photoreceptor degeneration (PRD) is a genetically heterogeneous retinal disorder. Although a number of genes involved in PRD have been identified, their genetic basis remains unknown in a significant number of patients. In this study, we aimed to identify novel disease-causing genes of PRD.

METHODS: Comprehensive ocular examinations were performed in a 2-year-old patient diagnosed with early onset PRD. Retinal capture sequencing was performed to screen causative mutations in known retinal disease-causing loci. Whole-exome sequencing (WES) and a series of variant-filtering strategies were applied for identifying novel disease-causing genes. Retina ATF6 expression was confirmed by immunohistochemistry. RT-PCR was performed to identify ATF6 mRNA in the patient.

RESULTS: The patient showed typical PRD features, with macular involvement and ellipsoid zone irregularities. Results of retinal capture sequencing were negative. WES data led to identification of biallelic loss-of-function mutations in the ATF6 gene. The first variant generates a premature stop codon (NCBI accession no. NM_007348: c.1126C>T, p.R376*) and the second variant affects a splicing donor site (NM_007348: c.1533+1G>C). Sanger sequencing confirmed the 2 alleles are from 1 parent each. Both of the variants are extremely rare in the population. The splicing variant causes either intron inclusion or exon skipping in the patient, thus severely disrupting ATF6 functional domains. ATF6 is expressed in three neuronal cell layers of mouse retina.

CONCLUSIONS: Our results support ATF6 as a novel disease-causing gene for PRD and suggest that disrupted protein quality control mechanisms may be a novel pathological mechanism underlying human retinal degeneration.

%B Invest Ophthalmol Vis Sci %V 56 %P 3889-95 %8 2015 Jun %G eng %N 6 %1 https://www.ncbi.nlm.nih.gov/pubmed/26070061?dopt=Abstract %R 10.1167/iovs.15-16778 %0 Journal Article %J Hum Genet %D 2015 %T Mutations in human IFT140 cause non-syndromic retinal degeneration. %A Xu, Mingchu %A Yang, Lizhu %A Wang, Feng %A Li, Huajin %A Wang, Xia %A Wang, Weichen %A Ge, Zhongqi %A Wang, Keqing %A Zhao, Li %A Li, Hui %A Li, Yumei %A Sui, Ruifang %A Chen, Rui %K Adult %K Amino Acid Sequence %K Carrier Proteins %K Child %K Female %K Genetic Association Studies %K Humans %K Leber Congenital Amaurosis %K Male %K Middle Aged %K Mutation, Missense %K Pedigree %K Retinitis Pigmentosa %X

Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) are two genetically heterogeneous retinal degenerative disorders. Despite the identification of a number of genes involved in LCA and RP, the genetic etiology remains unknown in many patients. In this study, we aimed to identify novel disease-causing genes of LCA and RP. Retinal capture sequencing was initially performed to screen mutations in known disease-causing genes in different cohorts of LCA and RP patients. For patients with negative results, we performed whole exome sequencing and applied a series of variant filtering strategies. Sanger sequencing was done to validate candidate causative IFT140 variants. Exome sequencing data analysis led to the identification of IFT140 variants in multiple unrelated non-syndromic LCA and RP cases. All the variants are extremely rare and predicted to be damaging. All the variants passed Sanger validation and segregation tests provided that the family members' DNA was available. The results expand the phenotype spectrum of IFT140 mutations to non-syndromic retinal degeneration, thus extending our understanding of intraflagellar transport and primary cilia biology in the retina. This work also improves the molecular diagnosis of retinal degenerative disease.

%B Hum Genet %V 134 %P 1069-78 %8 2015 Oct %G eng %N 10 %1 https://www.ncbi.nlm.nih.gov/pubmed/26216056?dopt=Abstract %R 10.1007/s00439-015-1586-x %0 Journal Article %J Sci Rep %D 2015 %T NGS-based Molecular diagnosis of 105 eyeGENE(®) probands with Retinitis Pigmentosa. %A Ge, Zhongqi %A Bowles, Kristen %A Goetz, Kerry %A Scholl, Hendrik P N %A Wang, Feng %A Wang, Xinjing %A Xu, Shan %A Wang, Keqing %A Wang, Hui %A Chen, Rui %K Antigens, Neoplasm %K Cell Cycle Proteins %K Child %K Child, Preschool %K Cohort Studies %K Cytoskeletal Proteins %K Female %K Genetic Association Studies %K Genetic Testing %K High-Throughput Nucleotide Sequencing %K Humans %K Inheritance Patterns %K Male %K Molecular Diagnostic Techniques %K Mutation %K Neoplasm Proteins %K Pedigree %K Phenotype %K Receptors, G-Protein-Coupled %K Receptors, Glutamate %K Retinitis Pigmentosa %X

The National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE(®)) was established in an effort to facilitate basic and clinical research of human inherited eye disease. In order to provide high quality genetic testing to eyeGENE(®)'s enrolled patients which potentially aids clinical diagnosis and disease treatment, we carried out a pilot study and performed Next-generation sequencing (NGS) based molecular diagnosis for 105 Retinitis Pigmentosa (RP) patients randomly selected from the network. A custom capture panel was designed, which incorporated 195 known retinal disease genes, including 61 known RP genes. As a result, disease-causing mutations were identified in 52 out of 105 probands (solving rate of 49.5%). A total of 82 mutations were identified, and 48 of them were novel. Interestingly, for three probands the molecular diagnosis was inconsistent with the initial clinical diagnosis, while for five probands the molecular information suggested a different inheritance model other than that assigned by the physician. In conclusion, our study demonstrated that NGS target sequencing is efficient and sufficiently precise for molecular diagnosis of a highly heterogeneous patient cohort from eyeGENE(®).

%B Sci Rep %V 5 %P 18287 %8 2015 Dec 15 %G eng %1 https://www.ncbi.nlm.nih.gov/pubmed/26667666?dopt=Abstract %R 10.1038/srep18287