Targeted Sequencing of 179 Genes Associated with Hereditary Retinal Dystrophies and 10 Candidate Genes Identifies Novel and Known Mutations in Patients with Various Retinal Diseases

Chen, Xuejuan; Zhao, Kang; Sheng, Xunlun; Li, Yang; Gao, Xiang; Zhang, Xiumei; Kang, Xiaoli; Pan, Xinyuan; Liu, Yuan; Jiang, Chao; Shi, Handuo; Chen, Xue; Rong, Weining; Chen, Li Jia; Lai, Timothy Y. Y.; Liu, Yani; Wang, Xiuying; Yuan, Songtao; Liu, Qinghuai; Vollrath, Douglas; Pang, Chi Pui; Zhao, Chunxia

doi:10.1167/iovs.12-10967

Cited by 62 publications

(68 citation statements)

References 42 publications

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“…With respect to the use of custom-made resequencing arrays, one of their main features is that they are not restricted only to known genetic variants, but they can resequence and interrogate the entire gene including coding exons, untranslated regions and exon-flanking intron sequences of a high number of IRD genes. Nonetheless, apart from the high cost involved in this kind of arrays (1,000-1,500 EUR/patient), their diagnostic capacity power of likely pathogenic genetic variants in IRD patients is comparable to that obtained by our strategy, according to most of the recent studies, with detection rates ranging between 14 and 25% [39,47,48], with only 1 case with a detection rate of 56%, as far as we are aware of [49]. Moreover, this resequencing technology requires 2 very time-consuming steps: the design and testing of all primers representing the exons of the genes included in the arrays, and the handling and analysis of the huge amount of data generated in the process.…”

Section: Discussionsupporting

confidence: 67%

A Cost-Effective Mutation Screening Strategy for Inherited Retinal Dystrophies

Barandika

Irigoyen²,

Anasagasti³

et al. 2016

Ophthalmic Res

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Objective: We developed a simple, time- and cost-effective Excel-based genetic screening strategy for the diagnosis of inherited retinal dystrophies (IRD). Design: 76 patients diagnosed with IRD and 112 nonaffected family members, from 55 unrelated families, were included. DNA samples were analyzed using Axiom Exome Genotyping Array Plates (Affymetrix) that contain over 300,000 genetic variants, including more than 5,000 variants present in 181 genes involved in IRD. We used a simple Excel-based data mining strategy in order to screen IRD variants likely involved in the development of IRD. Results: A total of 5 relevant genetic variants were found in 5 IRD genes. Four variants were reported either as pathogenic or with a prediction of probably damaging, and 1 variant was reported to affect a regulatory region. These variants were present in 14 patients and in 11 carriers, in 10 unrelated families. Conclusion: Using our Excel-based data screening strategy, we were able to assign likely genetic diagnoses in a fast and cost-effective manner to over 18% of patients analyzed, with a comparable ratio of genetic findings to that reported with retina-specific arrays for about 1/5 of the cost. Our approach proved efficient in reducing costs and time for IRD diagnosis as a first tier genetic screening method.

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Section: Discussionsupporting

confidence: 67%

A Cost-Effective Mutation Screening Strategy for Inherited Retinal Dystrophies

Barandika

Irigoyen²,

Anasagasti³

et al. 2016

Ophthalmic Res

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“…41 Up to now, only one missense mutation in exon 8 of VCAN has been identified as the causative mutation in a family with autosomal dominant RP. 42 Furthermore, mutations in splice sites were reported as disease causing in families with Wagner syndrome (WS, OMIM #143200), a rare IRD with several symptoms related to RP. 43 Since the affected individuals in our family do not show typical features of WS, our results support to the hypothesis that mutations in the VCAN gene may result in different ophthalmic phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Exome Sequencing RevealsAGBL5as Novel Candidate Gene and Additional Variants for Retinitis Pigmentosa in Five Turkish Families

Kastner

Thiemann

Dekomien

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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“…Three advanced technologies using next-generation sequencing (NGS) are in use: targeted retinal-gene capture NGS (Simpson et al 2011; Audo et al 2012; Neveling et al 2012; O’Sullivan et al 2012; Chen et al 2013; Eisenberger et al 2013; Glockle et al 2013; Wang et al 2014), whole-exome NGS (Bowne et al 2011a; Ozgul et al 2011; Tucker et al 2011; Zeitz et al 2013; El Shamieh et al 2014; Jin et al 2014; Sergouniotis et al 2014), and whole-genome NGS (Nishiguchi et al 2013). Each has advantages and disadvantages.…”

Section: Finding Genes and Mutations Causing Adrpmentioning

confidence: 99%

Genes and Mutations Causing Autosomal Dominant Retinitis Pigmentosa

Daiger

Bowne

Sullivan

2014

Cold Spring Harb Perspect Med

109

140

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Retinitis pigmentosa (RP) has a prevalence of approximately one in 4000; 25%–30% of these cases are autosomal dominant retinitis pigmentosa (adRP). Like other forms of inherited retinal disease, adRP is exceptionally heterogeneous. Mutations in more than 25 genes are known to cause adRP, more than 1000 mutations have been reported in these genes, clinical findings are highly variable, and there is considerable overlap with other types of inherited disease. Currently, it is possible to detect disease-causing mutations in 50%–75% of adRP families in select populations. Genetic diagnosis of adRP has advantages over other forms of RP because segregation of disease in families is a useful tool for identifying and confirming potentially pathogenic variants, but there are disadvantages too. In addition to identifying the cause of disease in the remaining 25% of adRP families, a central challenge is reconciling clinical diagnosis, family history, and molecular findings in patients and families.

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Targeted Sequencing of 179 Genes Associated with Hereditary Retinal Dystrophies and 10 Candidate Genes Identifies Novel and Known Mutations in Patients with Various Retinal Diseases

Cited by 62 publications

References 42 publications

A Cost-Effective Mutation Screening Strategy for Inherited Retinal Dystrophies

A Cost-Effective Mutation Screening Strategy for Inherited Retinal Dystrophies

Exome Sequencing RevealsAGBL5as Novel Candidate Gene and Additional Variants for Retinitis Pigmentosa in Five Turkish Families

Genes and Mutations Causing Autosomal Dominant Retinitis Pigmentosa

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