New all-in-one protocol for 24-chromosome aneuploidies and monogenic diseases detection by next- generation sequencing: first-year experience

2018 ◽  
Vol 36 ◽  
pp. e34-e35
Author(s):  
Santiago González-Reig ◽  
Vanessa Penacho ◽  
Diego Amorós ◽  
Natalia Castejón-Fernández ◽  
Helena Blanca ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
First Year Experience ◽  
First Year ◽  
Next Generation ◽  
Monogenic Diseases ◽  
Generation Sequencing

scholarly journals Brain Tumor Biobank Development for Precision Medicine: Role of the Neurosurgeon

2021 ◽  
Vol 11 ◽  
Author(s):  
Emilie Darrigues ◽  
Benjamin W. Elberson ◽  
Annick De Loose ◽  
Madison P. Lee ◽  
Ebonye Green ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Next Generation Sequencing ◽  
Precision Medicine ◽  
Critical Role ◽  
First Year ◽  
Histopathological Diagnosis ◽  
Next Generation ◽  
Cancer Predisposition Syndrome ◽  
Generation Sequencing

Neuro-oncology biobanks are critical for the implementation of a precision medicine program. In this perspective, we review our first year experience of a brain tumor biobank with integrated next generation sequencing. From our experience, we describe the critical role of the neurosurgeon in diagnosis, research, and precision medicine efforts. In the first year of implementation of the biobank, 117 patients (Female: 62; Male: 55) had 125 brain tumor surgeries. 75% of patients had tumors biobanked, and 16% were of minority race/ethnicity. Tumors biobanked were as follows: diffuse gliomas (45%), brain metastases (29%), meningioma (21%), and other (5%). Among biobanked patients, 100% also had next generation sequencing. Eleven patients qualified for targeted therapy based on identification of actionable gene mutations. One patient with a hereditary cancer predisposition syndrome was also identified. An iterative quality improvement process was implemented to streamline the workflow between the operating room, pathology, and the research laboratory. Dedicated tumor bank personnel in the department of neurosurgery greatly improved standard operating procedure. Intraoperative selection and processing of tumor tissue by the neurosurgeon was integral to increasing success with cell culture assays. Currently, our institutional protocol integrates standard histopathological diagnosis, next generation sequencing, and functional assays on surgical specimens to develop precision medicine protocols for our patients. This perspective reviews the critical role of neurosurgeons in brain tumor biobank implementation and success as well as future directions for enhancing precision medicine efforts.

Diagnostic Approach to Monogenic Inflammatory Bowel Disease in Clinical Practice: A Ten-Year Multicentric Experience

2019 ◽  
Vol 26 (5) ◽  
pp. 720-727 ◽  
Author(s):  
Sara Lega ◽  
Alessia Pin ◽  
Serena Arrigo ◽  
Cristina Cifaldi ◽  
Martina Girardelli ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Next Generation Sequencing ◽  
Bowel Disease ◽  
Early Onset ◽  
Genetic Diagnosis ◽  
Diagnostic Approach ◽  
Next Generation ◽  
Monogenic Diseases ◽  
Inflammatory Bowel ◽  
Generation Sequencing

Abstract Background and aims Multiple monogenic disorders present as very early onset inflammatory bowel disease (VEO-IBD) or as IBD with severe and atypical features. Establishing a genetic diagnosis may change patients’ management and prognosis. In this study, we describe the diagnostic approach to suspected monogenic IBD in a real clinical setting, discussing genetic and phenotypic findings and therapeutic implications of molecular diagnosis. Methods Information of patients with VEO-IBD and early onset IBD with severe/atypical phenotypes (EO-IBD s/a) managed between 2008–2017 who underwent a genetic workup were collected. Results Ninety-three patients were included, and 12 (13%) reached a genetic diagnosis. Candidate sequencing (CS) was performed in 47 patients (50%), and next generation sequencing (NGS) was performed in 84 patients (90%). Candidate sequencing had a good diagnostic performance only when guided by clinical features specific for known monogenic diseases, whereas NGS helped finding new causative genetic variants and would have anticipated one monogenic diagnosis (XIAP) and consequent bone marrow transplant (BMT). Patients with monogenic IBD more frequently were male (92% vs 54%; P = 0.02), had extraintestinal findings (100% vs 34%; P < 0.001), and had disease onset ≤1 month of life (25% vs 1%; P = 0.006). Genetic diagnosis impacted patient management in 11 patients (92%), 7 of whom underwent BMT. Conclusion A genetic diagnosis can be established in a significant proportion of suspected monogenic IBD and has an impact on patients’ management. Candidate sequencing may be deployed when clinical findings orientate toward a specific diagnosis. Next generation sequencing should be preferred in patients with nonspecific phenotypes.

scholarly journals Live births after simultaneous avoidance of monogenic diseases and chromosome abnormality by next-generation sequencing with linkage analyses

2015 ◽  
Vol 112 (52) ◽  
pp. 15964-15969 ◽  
Author(s):  
Liying Yan ◽  
Lei Huang ◽  
Liya Xu ◽  
Jin Huang ◽  
Fei Ma ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Linkage Analysis ◽  
False Positive ◽  
Chromosome Abnormality ◽  
False Negative ◽  
Genetic Diagnosis ◽  
Next Generation ◽  
Linkage Analyses ◽  
Monogenic Diseases ◽  
Generation Sequencing

In vitro fertilization (IVF), preimplantation genetic diagnosis (PGD), and preimplantation genetic screening (PGS) help patients to select embryos free of monogenic diseases and aneuploidy (chromosome abnormality). Next-generation sequencing (NGS) methods, while experiencing a rapid cost reduction, have improved the precision of PGD/PGS. However, the precision of PGD has been limited by the false-positive and false-negative single-nucleotide variations (SNVs), which are not acceptable in IVF and can be circumvented by linkage analyses, such as short tandem repeats or karyomapping. It is noteworthy that existing methods of detecting SNV/copy number variation (CNV) and linkage analysis often require separate procedures for the same embryo. Here we report an NGS-based PGD/PGS procedure that can simultaneously detect a single-gene disorder and aneuploidy and is capable of linkage analysis in a cost-effective way. This method, called “mutated allele revealed by sequencing with aneuploidy and linkage analyses” (MARSALA), involves multiple annealing and looping-based amplification cycles (MALBAC) for single-cell whole-genome amplification. Aneuploidy is determined by CNVs, whereas SNVs associated with the monogenic diseases are detected by PCR amplification of the MALBAC product. The false-positive and -negative SNVs are avoided by an NGS-based linkage analysis. Two healthy babies, free of the monogenic diseases of their parents, were born after such embryo selection. The monogenic diseases originated from a single base mutation on the autosome and the X-chromosome of the disease-carrying father and mother, respectively.

Hereditary variant of diabetes mellitus caused by a defect of the NEUROD1 gene (MODY6): the first description in Russia

2016 ◽  
Vol 62 (3) ◽  
pp. 16-20 ◽  
Author(s):  
Olesya A. Gioeva ◽  
Anna A. Kolodkina ◽  
Evgeny V. Vasilyev ◽  
Vasiliy M. Petrov ◽  
Anatoly N. Tiulpakov
Keyword(s):  
Next Generation Sequencing ◽  
Molecular Genetic ◽  
Final Diagnosis ◽  
Regulation Of Transcription ◽  
Next Generation ◽  
Molecular Genetic Study ◽  
Inherited Disorders ◽  
Dominant Type ◽  
Monogenic Diseases ◽  
Generation Sequencing

MODY (Maturity-Onset diabetes of the young) is a heterogeneous group of disorders characterized by autosomal dominant type of inheritance and caused by genetic defects leading to dysfunction of pancreatic b-cells. Currently 13 candidate genes of MODY, and, respectively, 13 MODY subtypes are known. The final diagnosis can be established only on the basis of molecular genetic studies, which is the «gold standard» in the diagnosis of this disease. MODY2 and MODY3 are the most prevalent subtypes and were previously described in our country. Rare MODY subtypes have not been described in Russian literature. In this article we describe the first diagnosed case of MODY6 in Russia (a defect of the NEUROD1 gene, encoding neurogenic differentiation factor 1, which plays an important role in normal differentiation of β-cells of the pancreas and the regulation of transcription of the insulin gene). Molecular genetic study was conducted using the method of next-generation sequencing, has recently been widely used for genetic verification of monogenic diseases and, in particular, MODY. Technology of next-generation sequencing for diagnosing inherited disorders of carbohydrate metabolism in domestic practice used for the first time.

scholarly journals Clinical and molecular genetic characteristics of MODY cases with digenic and oligogenic inheritance as defined by targeted next-generation sequencing

2017 ◽  
Vol 62 (6) ◽  
pp. 20-27 ◽  
Author(s):  
Olesya A. Gioeva ◽  
Natalya A. Zubkova ◽  
Yulia V. Tikhonovich ◽  
Vasiliy M. Petrov ◽  
Evgeniy V. Vasilyev ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Analysis ◽  
Candidate Genes ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Simultaneous Analysis ◽  
Next Generation ◽  
Monogenic Diseases ◽  
Oligogenic Inheritance ◽  
Generation Sequencing

The diagnosis of MODY should be verified by molecular genetic analysis. Recently the introduction of next-generation sequencing, allowing simultaneous analysis of several candidate genes, greatly facilitates the diagnosis of monogenic diseases including MODY. In addition, the simultaneous analysis of several candidate genes allows to identify cases with digenic and oligogenic inheritance. In this work we present the first description of MODY cases with digenic and oligogenic inheritance in our country.Aim — to characterize MODY cases with digenic and oligogenic inheritance as defined by targeted next-generation sequencing.Material and methods. 256 subjects (age range, 0.3—25 yrs; males, n=149, females, n=107) were included in the study. The patients fulfilled the following MODY criteria: diabetes or intermediate hyperglycemia, absence of β-cell autoimmunity (ICA, GAD, IA2, IAA antibodies), preserved C-peptide secretion. Molecular genetic analysis was performed by next-generation sequencing using custom Ion Ampliseq gene panel and PGM semiconductor sequencer (Ion Torrent). All mutations were confirmed by Sanger sequencing.Results. 10 patients (8 probands, 1 sibling and 1 parent) showed digenic inheritance of MODY: 3 patients with combination of mutations in 2 candidate genes of MODY, 7 — in a candidate genes of MODY and another gene, associated with diabetes mellitus. In 1 case (sibling) showed oligogenic inheritance (mutations in GCK, HNF4A and INSR genes). Seven of the identified mutations were not previously described.Conclusion. Next-generation sequencing is useful in identifying of MODY cases with digenic and oligogenic inheritance, which is extremely important with potentially modifying effect on the phenotype.

Labordiagnostik bei gastrointestinalen Tumoren

2020 ◽  
Vol 11 (05) ◽  
pp. 232-238
Author(s):  
Marcus Kleber
Keyword(s):  
Next Generation Sequencing ◽  
Kolorektales Karzinom ◽  
Next Generation ◽  
Generation Sequencing

ZUSAMMENFASSUNGDas kolorektale Karzinom (KRK) ist einer der häufigsten malignen Tumoren in Deutschland. Einer frühzeitigen Diagnostik kommt große Bedeutung zu. Goldstandard ist hier die Koloskopie. Die aktuelle S3-Leitlinie Kolorektales Karzinom empfiehlt zum KRK-Screening den fäkalen okkulten Bluttest. Für das Monitoring von Patienten vor und nach Tumorresektion werden die Messung des Carcinoembryonalen Antigens (CEA) und der Mikrosatellitenstabilität empfohlen. Für die Auswahl der korrekten Chemotherapie scheint derzeit eine Überprüfung des Mutationsstatus, mindestens des KRAS-Gens und des BRAF-Gens, sinnvoll zu sein. Eine Reihe an neuartigen Tumormarkern befindet sich momentan in der Entwicklung, hat jedoch noch nicht die Reife für eine mögliche Anwendung in der Routinediagnostik erreicht. Den schnellsten Weg in die breite Anwendung können Next-Generation-Sequencing-basierte genetische Tests finden.

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