Identification of a novel variant of epsilon-gamma-delta-beta thalassemia highlights limitations of next generation sequencing

2015 ◽  
Vol 90 (3) ◽  
pp. E52-E54 ◽  
Author(s):  
Armin Zebisch ◽  
Eduard Schulz ◽  
Michela Grosso ◽  
Barbara Lombardo ◽  
Giovanni Acierno ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Beta Thalassemia ◽  
Next Generation ◽  
Gamma Delta ◽  
Novel Variant ◽  
Generation Sequencing

Novel variant blossom: From pathology to next generation sequencing to cellular biology

2015 ◽  
Vol 25 ◽  
pp. S298
Author(s):  
W. Zhu ◽  
S. Mitsuhashi ◽  
W. Liang ◽  
T. Ito ◽  
I. Nishino
Keyword(s):  
Next Generation Sequencing ◽  
Cellular Biology ◽  
Next Generation ◽  
Novel Variant ◽  
Generation Sequencing

scholarly journals Development and clinical application of a preimplantation genetic testing for monogenic disease (PGT-M) for beta thalassemia in Vietnam

2020 ◽  
Author(s):  
Anh Dao Mai ◽  
Gary L. Harton ◽  
Vinh Nguyen Quang ◽  
Huynh Nguyen Van ◽  
Nhung Hoang Thi ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Embryo Transfer ◽  
Clinical Application ◽  
Monogenic Disease ◽  
Beta Thalassemia ◽  
Next Generation ◽  
Whole Genome Analysis ◽  
Preimplantation Genetic Testing ◽  
Low Pass ◽  
Generation Sequencing

Abstract Purpose The purpose of this research is to study the clinical outcomes using a next-generation sequencing-based protocol allowing for simultaneous testing of mutations in the beta thalassemia (HBB) gene, including single nucleotide polymorphism (SNP) markers for PGT-M along with low-pass whole genome analysis of chromosome aneuploidies for PGT-A. Methods A combined PGT-M (thalassemia) plus PGT-A system was developed for patients undergoing IVF in Vietnam. Here we developed a system for testing numerous thalassemia mutations plus SNP-based testing for backup mutation analysis and contamination control using next-generation sequencing (NGS). Low -pass next-generation sequencing was used to assess aneuploidy in some of the clinical PGT cases. Patients underwent IVF followed by embryo biopsy at the blastocyst stage for combined PGT-A/M. Results Two cases have completed the entire process including transfer of embryos, while a further nine cases have completed the IVF and PGT-M/A analysis but have not completed embryo transfer. In the two cases with embryo transfer, both patients achieved pregnancy with an unaffected, euploid embryo confirmed through prenatal diagnosis. In the further nine cases, 39 embryos were biopsied and all passed QC for amplification. There were 8 unaffected embryos, 31 carrier embryos, and 11 affected embryos. A subset of 24 embryos also had PGT-A analysis with 22 euploid embryos and 2 aneuploid embryos. Conclusions Here we report the development and clinical application of a combined PGT-M for HBB and PGT-A for gross chromosome aneuploidies from 11 patients with detailed laboratory findings along with 2 cases that have completed embryo transfer.

scholarly journals Novel PAX6 variant in a family with ophthalmologic, pancreatic, and olfactory features

2021 ◽  
pp. mcs.a006149
Author(s):  
Kristen Lee Buehne ◽  
Sarah Hart ◽  
Bradley Williams ◽  
Jennifer L Cohen
Keyword(s):  
Genetic Testing ◽  
Next Generation Sequencing ◽  
Family Members ◽  
Clinical Findings ◽  
Young Age ◽  
Next Generation ◽  
Congenital Cataracts ◽  
Novel Variant ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Variants in the PAX6 gene have been associated with ophthalmologic, neurologic, and pancreatic differences. We report on a proband, mother, and affected brother who presented with congenital cataracts and glaucoma at a young age. Non-ocular findings are also reported among these family members. After a congenital cataracts next generation sequencing (NGS) gene panel was found to be non-diagnostic in 2016, a more expanded panel in 2020 revealed a novel variant: c.178T>A; p.Tyr60Asn in exon 6 of the PAX6 gene in the proband. The variant is also present in the affected mother and affected brother; it is absent in an unaffected brother. The clinical findings of these three relatives, in conjunction with their genetic testing and the associated PAX6 features reported in the literature, suggest that this novel familial variant may be an underlying etiology for these individuals' ophthalmologic, pancreatic, and olfactory symptoms.

Comprehensive Genetic Analysis of RASopathy in the Era of Next-Generation Sequencing and Definition of a Novel Likely Pathogenic KRAS Variation

2022 ◽  
pp. 1-11
Author(s):  
Selma Demir ◽  
Hümeyra Yaşar Köstek ◽  
Aslıhan Sanrı ◽  
Ruken Yıldırım ◽  
Fatma Özgüç Çömlek ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Mapk Pathway ◽  
Mutation Screening ◽  
Genetic Diagnosis ◽  
Next Generation ◽  
Patient Cohort ◽  
Genes Encoding ◽  
Novel Variant ◽  
Mutation Distribution ◽  
Generation Sequencing

<b><i>Introduction:</i></b> Germline pathogenic variations of the genes encoding the components of the Ras-MAPK pathway are found to be responsible for RASopathies, a clinically and genetically heterogeneous group of diseases. In this study, we aimed to present the results of patients genetically investigated for RASopathy-related mutations in our Genetic Diagnosis Center. <b><i>Methods:</i></b> The results of 51 unrelated probands with RASopathy and 4 affected relatives (31 male, 24 female; mean age: 9.327 ± 8.214) were included in this study. Mutation screening was performed on DNA samples from peripheral blood of the patients either by Sanger sequencing of <i>PTPN11</i> hotspot regions (10/51 probands), or by a targeted amplicon next-generation sequencing panel (41/51 probands) covering the exonic regions of <i>BRAF</i>, <i>CBL</i>, <i>HRAS</i>, <i>KRAS</i>, <i>LZTR1</i>, <i>MAP2K1</i>, <i>MAP2K2</i>, <i>NF1</i>, <i>NRAS</i>, <i>PTPN11</i>, <i>RAF1</i>, <i>RASA2</i>, <i>RIT1</i>, <i>SHOC2</i>, <i>SOS1</i>, <i>SOS2</i>, <i>SPRED1</i>, and <i>KAT6B</i> genes. <b><i>Results:</i></b> Pathogenic/likely pathogenic variations found in 22 out of 51 probands (43.13%) and their 4 affected family members were located in <i>PTPN11</i>, <i>BRAF</i>, <i>KRAS</i>, <i>NF1</i>, <i>RAF1</i>, <i>SOS1</i>, and <i>SHOC2</i> genes. The c.148A&#x3e;C (p.Thr50Pro) variation in the <i>KRAS</i> gene was a novel variant detected in a sibling in our patient cohort. We found supportive evidence for the pathogenicity of the <i>NF1</i> gene c.5606G&#x3e;T (p.Gly1869Val) variation which we defined in an affected boy who inherited the mutation from his affected father. <b><i>Conclusion:</i></b> Although <i>PTPN11</i> is the most frequently mutated gene in our patient cohort, as in most previous reports, different mutation distribution among the other genes studied motivates the use of a next-generation sequencing gene panel including the possible responsible genes.

scholarly journals Phenylketonuria Diagnosis by Massive Parallel Sequencing and Genotype-Phenotype Association in Brazilian Patients

Genes ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 20
Author(s):  
Rafael Hencke Tresbach ◽  
Fernanda Sperb-Ludwig ◽  
Rodrigo Ligabue-Braun ◽  
Tássia Tonon ◽  
Maria Teresinha de Oliveira Cardoso ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Phenylalanine Hydroxylase ◽  
Next Generation ◽  
Ion Torrent Pgm ◽  
Pathogenic Variants ◽  
Functionally Impaired ◽  
Novel Variant ◽  
The Stability ◽  
Pah Gene ◽  
Generation Sequencing

Phenylketonuria (PKU) is a common inborn error of amino acid metabolism in which the enzyme phenylalanine hydroxylase, which converts phenylalanine to tyrosine, is functionally impaired due to pathogenic variants in the PAH gene. Thirty-four Brazilian patients with a biochemical diagnosis of PKU, from 33 unrelated families, were analyzed through next-generation sequencing in the Ion Torrent PGM™ platform. Phenotype–genotype correlations were made based on the BioPKU database. Three patients required additional Sanger sequencing analyses. Twenty-six different pathogenic variants were identified. The most frequent variants were c.1315+1G>A (n = 8/66), c.473G>A (n = 6/66), and c.1162G>A (n = 6/66). One novel variant, c.524C>G (p.Pro175Arg), was found in one allele and was predicted as likely pathogenic by the American College of Medical Genetics and Genomics (ACMG) criteria. The molecular modeling of p.Pro175Arg indicated that this substitution can affect monomers binding in the PAH tetramer, which could lead to a change in the stability and activity of this enzyme. Next-generation sequencing was a fast and effective method for diagnosing PKU and is useful for patient phenotype prediction and genetic counseling.

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