Using next-generation sequencing for the diagnosis of rare disorders: a family with retinitis pigmentosa and skeletal abnormalities

2011 ◽  
Vol 225 (1) ◽  
pp. 12-18 ◽  
Author(s):  
Kasmintan A Schrader ◽  
Alireza Heravi-Moussavi ◽  
Paula J Waters ◽  
Janine Senz ◽  
James Whelan ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Retinitis Pigmentosa ◽  
Next Generation ◽  
Rare Disorders ◽  
Skeletal Abnormalities ◽  
Generation Sequencing

scholarly journals Next generation sequencing of pooled samples reveals new SNRNP200 mutations associated with retinitis pigmentosa

2011 ◽  
Vol 32 (6) ◽  
pp. E2246-E2258 ◽  
Author(s):  
Paola Benaglio ◽  
Terri L. McGee ◽  
Leonardo P. Capelli ◽  
Shyana Harper ◽  
Eliot L. Berson ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Retinitis Pigmentosa ◽  
Next Generation ◽  
Pooled Samples ◽  
Generation Sequencing

Next-generation sequencing and its application in diagnosis of retinitis pigmentosa

2019 ◽  
Vol 40 (5) ◽  
pp. 393-402 ◽  
Author(s):  
Arash Salmaninejad ◽  
Jamshid Motaee ◽  
Mahsa Farjami ◽  
Maliheh Alimardani ◽  
Alireza Esmaeilie ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Retinitis Pigmentosa ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Next-generation sequencing identifies unexpected genotype-phenotype correlations in patients with retinitis pigmentosa

PLoS ONE ◽  
2018 ◽  
Vol 13 (12) ◽  
pp. e0207958 ◽  
Author(s):  
Johannes Birtel ◽  
Martin Gliem ◽  
Elisabeth Mangold ◽  
Philipp L. Müller ◽  
Frank G. Holz ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Retinitis Pigmentosa ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Identification of 13 novel USH2A mutations in Chinese retinitis pigmentosa and Usher syndrome patients by targeted next-generation sequencing

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Ling-hui Qu ◽  
Xin Jin ◽  
Yan-ling Long ◽  
Jia-yun Ren ◽  
Chuang-huang Weng ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Retinitis Pigmentosa ◽  
Molecular Mechanisms ◽  
Usher Syndrome ◽  
Next Generation ◽  
Chinese Families ◽  
Targeted Next Generation Sequencing ◽  
Pathogenic Mutations ◽  
Basement Membrane Protein ◽  
Generation Sequencing

Abstract Background: The USH2A gene encodes usherin, a basement membrane protein that is involved in the development and homeostasis of the inner ear and retina. Mutations in USH2A are linked to Usher syndrome type II (USH II) and non-syndromic retinitis pigmentosa (RP). Molecular diagnosis can provide insight into the pathogenesis of these diseases, facilitate clinical diagnosis, and identify individuals who can most benefit from gene or cell replacement therapy. Here, we report 21 pathogenic mutations in the USH2A gene identified in 11 Chinese families by using the targeted next-generation sequencing (NGS) technology. Methods: In all, 11 unrelated Chinese families were enrolled, and NGS was performed to identify mutations in the USH2A gene. Variant analysis, Sanger validation, and segregation tests were utilized to validate the disease-causing mutations in these families. Results: We identified 21 pathogenic mutations, of which 13, including 5 associated with non-syndromic RP and 8 with USH II, have not been previously reported. The novel variants segregated with disease phenotype in the affected families and were absent from the control subjects. In general, visual impairment and retinopathy were consistent between the USH II and non-syndromic RP patients with USH2A mutations. Conclusions: These findings provide a basis for investigating genotype–phenotype relationships in Chinese USH II and RP patients and for clarifying the pathophysiology and molecular mechanisms of the diseases associated with USH2A mutations.

Identification of a Disease-Causing Mutation in a Chinese Patient with Retinitis Pigmentosa by Targeted Next-Generation Sequencing

2017 ◽  
Vol 27 (6) ◽  
pp. 791-796 ◽  
Author(s):  
Jianping Xiao ◽  
Xueqin Guo ◽  
Yong Wang ◽  
Mingkun Shao ◽  
Xiaoming Wei ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Retinitis Pigmentosa ◽  
Sanger Sequencing ◽  
Bioinformatics Analysis ◽  
Family Members ◽  
Chinese Patient ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Targeted Ngs ◽  
Generation Sequencing

Purpose To identify disease-causing mutations in a Chinese patient with retinitis pigmentosa (RP). Methods A detailed clinical examination was performed on the proband. Targeted next-generation sequencing (NGS) combined with bioinformatics analysis was performed on the proband to detect candidate disease-causing mutations. Sanger sequencing was performed on all subjects to confirm the candidate mutations and assess cosegregation within the family. Results Clinical examinations of the proband showed typical characteristics of RP. Three candidate heterozygous mutations in 3 genes associated with RP were detected in the proband by targeted NGS. The 3 mutations were confirmed by Sanger sequencing and the deletion (c.357_358delAA) in PRPF31 was shown to cosegregate with RP phenotype in 7 affected family members, but not in 3 unaffected family members. Conclusions The deletion (c.357_358delAA) in PRPF31 was the disease-causing mutation for the proband and his affected family members with RP. To our knowledge, this is the second report of the deletion and the first report of the other 2 mutations in the Chinese population. Targeted NGS combined with bioinformatics analysis proved to be an effective molecular diagnostic tool for RP.

scholarly journals Whole Exome Sequencing Reveals Genetic Predisposition in a Large Family with Retinitis Pigmentosa

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Juan Wu ◽  
Lijia Chen ◽  
Oi Sin Tam ◽  
Xiu-Feng Huang ◽  
Chi-Pui Pang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Retinitis Pigmentosa ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Direct Sequencing ◽  
Genetic Defect ◽  
Chinese Family ◽  
Next Generation ◽  
Whole Exome ◽  
Generation Sequencing

Next-generation sequencing has become more widely used to reveal genetic defect in monogenic disorders. Retinitis pigmentosa (RP), the leading cause of hereditary blindness worldwide, has been attributed to more than 67 disease-causing genes. Due to the extreme genetic heterogeneity, using general molecular screening alone is inadequate for identifying genetic predispositions in susceptible individuals. In order to identify underlying mutation rapidly, we utilized next-generation sequencing in a four-generation Chinese family with RP. Two affected patients and an unaffected sibling were subjected to whole exome sequencing. Through bioinformatics analysis and direct sequencing confirmation, we identified p.R135W transition in the rhodopsin gene. The mutation was subsequently confirmed to cosegregate with the disease in the family. In this study, our results suggest that whole exome sequencing is a robust method in diagnosing familial hereditary disease.

scholarly journals Identification of a Novel Heterozygous Missense Mutation in theCACNA1FGene in a Chinese Family with Retinitis Pigmentosa by Next Generation Sequencing

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Qi Zhou ◽  
Jingliang Cheng ◽  
Weichan Yang ◽  
Mousumi Tania ◽  
Hui Wang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Retinitis Pigmentosa ◽  
Missense Mutation ◽  
Clinical Signs ◽  
Chinese Family ◽  
Next Generation ◽  
Heterozygous Missense Mutation ◽  
Peripheral Leukocytes ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Background.Retinitis pigmentosa (RP) is an inherited retinal degenerative disease, which is clinically and genetically heterogeneous, and the inheritance pattern is complex. In this study, we have intended to study the possible association of certain genes with X-linked RP (XLRP) in a Chinese family.Methods.A Chinese family with RP was recruited, and a total of seven individuals were enrolled in this genetic study. Genomic DNA was isolated from peripheral leukocytes, and used for the next generation sequencing (NGS).Results.The affected individual presented the clinical signs of XLRP. A heterozygous missense mutation (c.1555C>T, p.R519W) was identified by NGS in exon 13 of theCACNA1Fgene on X chromosome, and was confirmed by Sanger sequencing. It showed perfect cosegregation with the disease in the family. The mutation at this position in theCACNA1Fgene of RP was found novel by database searching.Conclusion.By using NGS, we have found a novel heterozygous missense mutation (c.1555C>T, p.R519W) inCACNA1Fgene, which is probably associated with XLRP. The findings might provide new insights into the cause and diagnosis of RP, and have implications for genetic counseling and clinical management in this family.

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