scholarly journals Next-generation sequencing reveals three novel variants in Polish patients with Usher syndrome

Klinika Oczna ◽  
2018 ◽  
Vol 2018 (4) ◽  
pp. 189-194
Author(s):  
Anna Wawrocka ◽  
Joanna Walczak-Sztulpa ◽  
Anna Skorczyk-Werner ◽  
Łukasz Kuszel ◽  
Magdalena Socha ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Usher Syndrome ◽  
Next Generation ◽  
Novel Variants ◽  
Generation Sequencing

Molecular genetic diagnosis by next-generation sequencing in a cohort of Mexican patients with haemophilia and report of novel variants

2020 ◽  
Vol 83 ◽  
pp. 102423 ◽  
Author(s):  
Laura Villarreal-Martínez ◽  
Marisol Ibarra-Ramirez ◽  
Geovana Calvo-Anguiano ◽  
José de Jesús Lugo-Trampe ◽  
Hilda Luna-Záizar ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Next Generation ◽  
Novel Variants ◽  
Molecular Genetic Diagnosis ◽  
Generation Sequencing ◽  
Mexican Patients

scholarly journals Next Generation Sequencing Identifies Five Novel Mutations in Lebanese Patients with Bardet–Biedl and Usher Syndromes

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 1047 ◽  
Author(s):  
Lama Jaffal ◽  
Wissam H Joumaa ◽  
Alexandre Assi ◽  
Charles Helou ◽  
George Cherfan ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Usher Syndrome ◽  
Bioinformatic Analysis ◽  
Next Generation ◽  
Novel Mutations ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Targeted Ngs ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Aim: To identify disease-causing mutations in four Lebanese families: three families with Bardet–Biedl and one family with Usher syndrome (BBS and USH respectively), using next generation sequencing (NGS). Methods: We applied targeted NGS in two families and whole exome sequencing (WES) in two other families. Pathogenicity of candidate mutations was evaluated according to frequency, conservation, in silico prediction tools, segregation with disease, and compatibility with inheritance pattern. The presence of pathogenic variants was confirmed via Sanger sequencing followed by segregation analysis. Results: Most likely disease-causing mutations were identified in all included patients. In BBS patients, we found (M1): c.2258A > T, p. (Glu753Val) in BBS9, (M2): c.68T > C; p. (Leu23Pro) in ARL6, (M3): c.265_266delTT; p. (Leu89Valfs*11) and (M4): c.880T > G; p. (Tyr294Asp) in BBS12. A previously known variant (M5): c.551A > G; p. (Asp184Ser) was also detected in BBS5. In the USH patient, we found (M6): c.188A > C, p. (Tyr63Ser) in CLRN1. M2, M3, M4, and M6 were novel. All of the candidate mutations were shown to be likely disease-causing through our bioinformatic analysis. They also segregated with the corresponding phenotype in available family members. Conclusion: This study expanded the mutational spectrum and showed the genetic diversity of BBS and USH. It also spotlighted the efficiency of NGS techniques in revealing mutations underlying clinically and genetically heterogeneous disorders.

scholarly journals A universal primer-independent next-generation sequencing approach for investigations of norovirus outbreaks and novel variants

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Jannik Fonager ◽  
Marc Stegger ◽  
Lasse Dam Rasmussen ◽  
Mille Weismann Poulsen ◽  
Jesper Rønn ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Next Generation ◽  
Universal Primer ◽  
Novel Variants ◽  
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.

scholarly journals αIIbβ3 variants defined by next-generation sequencing: Predicting variants likely to cause Glanzmann thrombasthenia

2015 ◽  
Vol 112 (15) ◽  
pp. E1898-E1907 ◽  
Author(s):  
Lorena Buitrago ◽  
Augusto Rendon ◽  
Yupu Liang ◽  
Ilenia Simeoni ◽  
Ana Negri ◽  
...  
Keyword(s):  
Amino Acids ◽  
Next Generation Sequencing ◽  
Hek293 Cells ◽  
Next Generation ◽  
Glanzmann Thrombasthenia ◽  
Missense Variants ◽  
Sorting Intolerant From Tolerant ◽  
Fibrinogen Binding ◽  
Novel Variants ◽  
Generation Sequencing

Next-generation sequencing is transforming our understanding of human genetic variation but assessing the functional impact of novel variants presents challenges. We analyzed missense variants in the integrin αIIbβ3 receptor subunit genes ITGA2B and ITGB3 identified by whole-exome or -genome sequencing in the ThromboGenomics project, comprising ∼32,000 alleles from 16,108 individuals. We analyzed the results in comparison with 111 missense variants in these genes previously reported as being associated with Glanzmann thrombasthenia (GT), 20 associated with alloimmune thrombocytopenia, and 5 associated with aniso/macrothrombocytopenia. We identified 114 novel missense variants in ITGA2B (affecting ∼11% of the amino acids) and 68 novel missense variants in ITGB3 (affecting ∼9% of the amino acids). Of the variants, 96% had minor allele frequencies (MAF) < 0.1%, indicating their rarity. Based on sequence conservation, MAF, and location on a complete model of αIIbβ3, we selected three novel variants that affect amino acids previously associated with GT for expression in HEK293 cells. αIIb P176H and β3 C547G severely reduced αIIbβ3 expression, whereas αIIb P943A partially reduced αIIbβ3 expression and had no effect on fibrinogen binding. We used receiver operating characteristic curves of combined annotation-dependent depletion, Polyphen 2-HDIV, and sorting intolerant from tolerant to estimate the percentage of novel variants likely to be deleterious. At optimal cut-off values, which had 69–98% sensitivity in detecting GT mutations, between 27% and 71% of the novel αIIb or β3 missense variants were predicted to be deleterious. Our data have implications for understanding the evolutionary pressure on αIIbβ3 and highlight the challenges in predicting the clinical significance of novel missense variants.

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