scholarly journals Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions

Brain ◽  
2012 ◽  
Vol 135 (11) ◽  
pp. 3404-3415 ◽  
Author(s):  
D. Ronchi ◽  
C. Garone ◽  
A. Bordoni ◽  
P. Gutierrez Rios ◽  
S. E. Calvo ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Next Generation Sequencing ◽  
Adult Patients ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals A Method for Next-Generation Sequencing of Paired Diagnostic and Remission Samples to Detect Mitochondrial DNA Mutations Associated with Leukemia

2017 ◽  
Vol 19 (5) ◽  
pp. 711-721 ◽  
Author(s):  
Ilaria S. Pagani ◽  
Chung H. Kok ◽  
Verity A. Saunders ◽  
Mark B. Van der Hoek ◽  
Susan L. Heatley ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Next Generation Sequencing ◽  
Next Generation ◽  
Mitochondrial Dna Mutations ◽  
Dna Mutations ◽  
Generation Sequencing

SAT0531 NEXT GENERATION SEQUENCING AND AUTOINFLAMMATORY SYNDROMES: CLINICAL AND GENETICAL CORRELATION ON AN ADULT POPULATION FROM A REFERRAL THIRD-CARE CENTRE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1223-1223
Author(s):  
J. R. Marques Soares ◽  
M. Antolin Mate ◽  
E. Garcia Arumi ◽  
E. Tizzano Ferrari ◽  
S. Bujan Rivas
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Data ◽  
Clinical Suspicion ◽  
Gene Panel ◽  
Adult Patients ◽  
Next Generation ◽  
Related Gene ◽  
Unknown Significance ◽  
Level Hospital ◽  
Generation Sequencing

Background:Systemic autoinflammatory diseases (sAID) are a group of conditions with recurrent episodes of inflammation in absence of infection or autoimmune response. Its physiopathology mainly lies on mono/poligenic mutations involving genes related to the innate immune system response. Next Generation Sequencing (NGS) platformss have been a big step forward on sAID diagnosis, although a clinical and genetic correlation is still needed.Objectives:To review the sAID related gene panel variants identified using NGS sAID gene panel on a cohort of adult patients screened for sAID from a referral third-level hospital.To correlate genetic and clinical findings for sAID related variants identified in order to the clinical suspicion diagnosis of sAID.Methods:A retrospective review of a cohort of adult (≥ 16 yo) patients with available NGS sAID related gene panel (MiSeq Illumina sequencing platform including intron and exon variants from up to 17 sAID genes, with coverage depth > x100) among 2014 and 2019 was performed.Demographic, clinical and genetic data were collected in a database.Genetic variants were classified according to the American College of Medical Genetics/Association for Molecular Pathology classification as benign/likely benign/variable of unknown significance (VUS)/likely pathogenic/pathogenic. In case of polymorphisms or lack of genetic data, the variants were named as unclassified.A description of the cohort and an analysis of the correlation assessment between clinical data and genetic findings were performed.Results:246 out of 299 (82%) patients with NGS sAID gene panel had clinical data available. 170/246 (69%) were adult patients. The medium age was 48 yo, and the M/F ratio was 2.46. 87/170 (51%) adult patients presented 122 variants involving sAID genes (60/87 patients with a single variant). All the variants out of 7 seven were heterozygous variants.Variants were classified according to ACMG/AMP as follow: pathogenic/probably pathogenic: 22/122 (18%), unknown significance: 74/122 (60.6%), benign/probably benign: 6/122 (4.91%). 20/122 (16.4%) were unclassified variants or polymorphisms.The most frequent variants identified involved MEFV (54/122), NOD2/CARD15 (18/122) and TNFRSF1A (17/122 including 12 p.Arg121Gln variants) genes.37/122 (30%) variants correlated with the clinical picture in 33 patients, allowing to confirm the suspected diagnosis. Among the 122 variants, 7 not previously communicated variants were identified.No somatic variants were found.Conclusion:NGS sAID related gene panel is a useful tool for sAID diagnosis. In this cohort of 170 adult patients from a referral third-level hospital, genetic tests identified sAID related variants in almost half of them.20% of patients who underwent genetic NGS sAID related gene panel studies were finally diagnosed with sAID.The identification of a genetic variant (even pathogenic / likely pathogenic variant) is not diagnostic for sAID if there is not a suggestive clinical picture.Despite genetic findings, a careful evaluation of clinical – genetic correlation is needed to confirm the suspicion diagnosis, especially for low penetrance variants like TNFRSF1A p. Arg121Gln.References:Diagnostic utility of a targeted next-generation sequencing gene panel in the clinical suspicion of systemic autoinflammatory diseases: a multi-center study. Karacan I, Balamir A, Uğurlu S, et al. . Rheumatol Int. 2019 May;39(5):911-919. doi: 10.1007/s00296-019-04252-5. Epub 2019 Feb 19.Disclosure of Interests:None declared

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