scholarly journals Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 539
Author(s):  
Lidia Gonzalez-Quereda ◽  
Maria Jose Rodriguez ◽  
Jordi Diaz-Manera ◽  
Jorge Alonso-Perez ◽  
Eduard Gallardo ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Neuromuscular Disorders ◽  
Neuromuscular Disorder ◽  
Gene Panel ◽  
Muscular Dystrophies ◽  
Next Generation ◽  
Congenital Myasthenic Syndromes ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing ◽  
Myasthenic Syndromes

The term neuromuscular disorder (NMD) includes many genetic and acquired diseases and differential diagnosis can be challenging. Next-generation sequencing (NGS) is especially useful in this setting given the large number of possible candidate genes, the clinical, pathological, and genetic heterogeneity, the absence of an established genotype-phenotype correlation, and the exceptionally large size of some causative genes such as TTN, NEB and RYR1. We evaluated the diagnostic value of a custom targeted next-generation sequencing gene panel to study the mutational spectrum of a subset of NMD patients in Spain. In an NMD cohort of 207 patients with congenital myopathies, distal myopathies, congenital and adult-onset muscular dystrophies, and congenital myasthenic syndromes, we detected causative mutations in 102 patients (49.3%), involving 42 NMD-related genes. The most common causative genes, TTN and RYR1, accounted for almost 30% of cases. Thirty-two of the 207 patients (15.4%) carried variants of uncertain significance or had an unidentified second mutation to explain the genetic cause of the disease. In the remaining 73 patients (35.3%), no candidate variant was identified. In combination with patients’ clinical and myopathological data, the custom gene panel designed in our lab proved to be a powerful tool to diagnose patients with myopathies, muscular dystrophies and congenital myasthenic syndromes. Targeted NGS approaches enable a rapid and cost-effective analysis of NMD- related genes, offering reliable results in a short time and relegating invasive techniques to a second tier.

scholarly journals Targeted next generation sequencing with an extended gene panel does not impact variant detection in mitochondrial diseases

2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Morgane Plutino ◽  
Annabelle Chaussenot ◽  
Cécile Rouzier ◽  
Samira Ait-El-Mkadem ◽  
Konstantina Fragaki ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Mitochondrial Diseases ◽  
Gene Panel ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Variant Detection ◽  
Generation Sequencing

scholarly journals Synchronous Pulmonary Adenocarcinomas

2020 ◽  
Vol 154 (1) ◽  
pp. 57-69
Author(s):  
Carlos A Pagan ◽  
Catherine A Shu ◽  
John P Crapanzano ◽  
Galina G Lagos ◽  
Mark B Stoopler ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Gene Panel ◽  
Driver Mutations ◽  
Molecular Testing ◽  
Next Generation ◽  
Synchronous Tumors ◽  
Targeted Next Generation Sequencing ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Objectives To determine concordance/discordance between morphology and molecular testing (MT) among synchronous pulmonary carcinomas using targeted next generation sequencing (NGS), with and without comprehensive molecular review (CMR), vs analyses of multiple singe genes (non-NGS). Methods Results of morphologic and MT assessment were classified as concordant, discordant, or indeterminate. For discordant cases, comprehensive histologic assessment (CHA) was performed. Results Forty-seven cases with 108 synchronous tumors were identified and underwent MT (NGS, n = 23 and non-NGS, n = 24). Histology and MT were concordant, discordant, and indeterminate in 53% (25/47), 21% (10/47), and 26% (12/47) of cases, respectively. CHA of the 10 discordant cases revised results of three cases. Conclusions There is discordance between histology and MT in a subset of cases and MT provides an objective surrogate for staging synchronous tumors. A limited gene panel is sufficient for objectively assessing a relationship if the driver mutations are distinct. Relatedness of mutations require CMR with a larger NGS panel (eg, 50 genes).

SAT0010 A Targeted Next-Generation Sequencing Gene Panel for Autoinflammation

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 667.2-667 ◽  
Author(s):  
E. Omoyinmi ◽  
A. Standing ◽  
A. Keylock ◽  
D. Rowczenio ◽  
S. Melo Gomes ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Gene Panel ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

scholarly journals Clinical impact of a targeted next-generation sequencing gene panel for autoinflammation and vasculitis

PLoS ONE ◽  
2017 ◽  
Vol 12 (7) ◽  
pp. e0181874 ◽  
Author(s):  
Ebun Omoyinmi ◽  
Ariane Standing ◽  
Annette Keylock ◽  
Fiona Price-Kuehne ◽  
Sonia Melo Gomes ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Clinical Impact ◽  
Gene Panel ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

scholarly journals GP.03 Diagnostic yield of next generation sequencing and myositis autoantibody panels in patients with axial myopathy

2019 ◽  
Vol 46 (s1) ◽  
pp. S6
Author(s):  
A Parks ◽  
J Karamchandani ◽  
Y Troyanov ◽  
R Massie ◽  
EK O’Ferrall
Keyword(s):  
Genetic Testing ◽  
Next Generation Sequencing ◽  
Muscle Biopsy ◽  
Diagnostic Yield ◽  
Neuromuscular Disorder ◽  
Next Generation ◽  
Antibody Testing ◽  
Initial Manifestation ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

Background: Axial myopathy is a rare neuromuscular disorder of variable etiology characterised by preferential involvement of the paraspinal muscles. We reviewed clinical features of patients with axial myopathies and the diagnostic yield of myositis-associated antibodies and targeted next generation sequencing panels. Methods: We performed a retrospective review of patients presenting with axial myopathy at the Montreal Neurological Hospital from 2011-2018. Data collection included clinical presentation, disease course, results of electromyography, imaging, laboratory and genetic testing, and histopathology on muscle biopsy. Results: Twenty-five patients were identified. Initial manifestation of axial weakness was head drop (15), camptocormia (8), and rigid spine (2). Autoimmune myositis was diagnosed in 9 patients, seropositive in 7 out of 7 tested for myositis-associated antibodies. Genetic testing was consistent with oculopharyngeal muscular dystrophy in one patient and RYR-1 (ryanodine receptor 1) related core myopathy in another. Local radiotherapy or spine surgery preceded the onset of axial weakness in 1 and 6 patients, respectively. Muscle biopsies were available in 17 patients and revealed myopathic changes (16), inflammatory changes (6), and myopathy with vacuoles (3). Conclusions: Recent advancements in genetic and antibody testing, combined with paraspinal muscle biopsy, allow for more precise classification and identification of potentially treatable axial myopathies.

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