scholarly journals Genetic diagnosis of familial hypercholesterolaemia by targeted next-generation sequencing

2014 ◽  
Vol 276 (4) ◽  
pp. 396-403 ◽  
Author(s):  
C. Maglio ◽  
R. M. Mancina ◽  
B. M. Motta ◽  
M. Stef ◽  
C. Pirazzi ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Familial Hypercholesterolaemia ◽  
Genetic Diagnosis ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

Evaluation of targeted next-generation sequencing–based preimplantation genetic diagnosis of monogenic disease

2013 ◽  
Vol 99 (5) ◽  
pp. 1377-1384.e6 ◽  
Author(s):  
Nathan R. Treff ◽  
Anastasia Fedick ◽  
Xin Tao ◽  
Batsal Devkota ◽  
Deanne Taylor ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Preimplantation Genetic Diagnosis ◽  
Genetic Diagnosis ◽  
Monogenic Disease ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

scholarly journals Compound Heterozygous Mutations in TMC1 and MYO15A Are Associated with Autosomal Recessive Nonsyndromic Hearing Loss in Two Chinese Han Families

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Pengcheng Xu ◽  
Jun Xu ◽  
Hu Peng ◽  
Tao Yang
Keyword(s):  
Hearing Loss ◽  
Next Generation Sequencing ◽  
Genetic Diagnosis ◽  
Compound Heterozygous ◽  
Next Generation ◽  
Chinese Han ◽  
Targeted Next Generation Sequencing ◽  
Recessive Mutations ◽  
Compound Heterozygous Mutations ◽  
Generation Sequencing

Genetic hearing loss is a common sensory disorder, and its cause is highly heterogeneous. In this study, by targeted next-generation sequencing of 414 known deafness genes, we identified compound heterozygous mutations p.R34X/p.M413T in TMC1 and p.S3417del/p.R1407T in MYO15A in two recessive Chinese Han deaf families. Intrafamilial cosegregation of the mutations with the hearing phenotype was confirmed in both families by the Sanger sequencing. Auditory features of the affected individuals are consistent with that previously reported for recessive mutations in TMC1 and MYO15A. The two novel mutations identified in this study, p.M413T in TMC1 and p.R1407T in MYO15A, are classified as likely pathogenic according to the guidelines of ACMG. Our study expanded the mutation spectrums of TMC1 and MYO15A and illustrated that genotype-phenotype correlation in combination with next-generation sequencing may improve the accuracy for genetic diagnosis of deafness.

scholarly journals Positive Impact of Expert Reference Center Validation on Performance of Next-Generation Sequencing for Genetic Diagnosis of Autoinflammatory Diseases

2019 ◽  
Vol 8 (10) ◽  
pp. 1729
Author(s):  
Boursier ◽  
Rittore ◽  
Georgin-Lavialle ◽  
Belot ◽  
Galeotti ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Diagnostic Performance ◽  
Positive Impact ◽  
Genetic Diagnosis ◽  
Autoinflammatory Diseases ◽  
Expert Advice ◽  
Next Generation ◽  
Reference Center ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

Monogenic autoinflammatory diseases (AIDs) are caused by variants in genes that regulate innate immunity. The current diagnostic performance of targeted next-generation sequencing (NGS) for AIDs is low. We assessed whether pre-analytic advice from expert clinicians could help improve NGS performance from our 4 years of experience with the sequencing of a panel of 55 AIDs genes. The study included all patients who underwent routine NGS testing between September 2014 and January 2019 at the laboratory of autoinflammatory diseases (Montpellier, France). Before March 2018, all medical requests for testing were accepted. After this time, we required validation by a reference center before NGS: the positive advice could be obtained after a face-to-face consultation with the patient or presentation of the patient’s case at a multidisciplinary staff meeting. Targeted NGS resulted in an overall 7% genetic confirmation, which is consistent with recent reports. The diagnostic performance before and after implementation of the new pre-requisite increased from 6% to 10% (p = 0.021). Our study demonstrated, for the first time, the beneficial effect of a two-step strategy (clinical expert advice, then genetic testing) for AIDs diagnosis and stressed the possible usefulness of the strategy in anticipation of the development of pan-genomic analyses in routine settings.

scholarly journals Genetic landscape of pediatric movement disorders and management implications

2018 ◽  
Vol 4 (5) ◽  
pp. e265 ◽  
Author(s):  
Dawn Cordeiro ◽  
Garrett Bullivant ◽  
Komudi Siriwardena ◽  
Andrea Evans ◽  
Jeff Kobayashi ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Movement Disorder ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Movement Disorders ◽  
Genetic Diagnosis ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Whole Exome ◽  
Generation Sequencing

ObjectiveTo identify underlying genetic causes in patients with pediatric movement disorders by genetic investigations.MethodsAll patients with a movement disorder seen in a single Pediatric Genetic Movement Disorder Clinic were included in this retrospective cohort study. We reviewed electronic patient charts for clinical, neuroimaging, biochemical, and molecular genetic features. DNA samples were used for targeted direct sequencing, targeted next-generation sequencing, or whole exome sequencing.ResultsThere were 51 patients in the Pediatric Genetic Movement Disorder Clinic. Twenty-five patients had dystonia, 27 patients had ataxia, 7 patients had chorea-athetosis, 8 patients had tremor, and 7 patients had hyperkinetic movements. A genetic diagnosis was confirmed in 26 patients, including in 20 patients with ataxia and 6 patients with dystonia. Targeted next-generation sequencing panels confirmed a genetic diagnosis in 9 patients, and whole exome sequencing identified a genetic diagnosis in 14 patients.ConclusionsWe report a genetic diagnosis in 26 (51%) patients with pediatric movement disorders seen in a single Pediatric Genetic Movement Disorder Clinic. A genetic diagnosis provided either disease-specific treatment or effected management in 10 patients with a genetic diagnosis, highlighting the importance of early and specific diagnosis.

scholarly journals Diagnostic Utility of Targeted Next Generation Sequencing in Patients with Vascular Anomalies

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 8-9
Author(s):  
Whitney Eng ◽  
Sophie Dilek ◽  
Abigail Ward ◽  
Harry PW Kozakewich ◽  
Alyaa Al-Ibraheemi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Next Generation Sequencing ◽  
Dna Sequences ◽  
Cancer Genomics ◽  
Massively Parallel Sequencing ◽  
Genetic Diagnosis ◽  
Vascular Anomalies ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

Background: Vascular anomalies are diverse entities and can range in severity from self-limiting to life-threatening. Diagnosis and care of these patients is challenging due to overlapping clinical and histologic features. Recently, it has been established that many vascular anomalies arise from somatic mutations in cancer genes (PIK3CA, AKT, NRAS). Use of cancer genomics in patients with vascular anomalies may establish a genetic diagnosis and expand use of targeted medical therapies. We evaluated the utility of targeted next generation sequencing for vascular anomalies patients at a single pediatric center. Methods: Using OncoPanel, a hybrid-capture and massively parallel sequencing assay that surveys DNA sequences of 447 genes implicated in cancer, we analyzed genetic variants in lesional tissue from vascular anomalies patients evaluated at Boston Children's Hospital between 5/2/2017 and 3/23/2020. Results: A total of 276 patients were consented and sequenced under the Dana Farber Cancer Institute Profile protocols DFCI 11-104 (n= 68) and DFCI 17-000 (n= 208). Clinical diagnoses prior to testing were varied and 11 patients (7%) had an unknown diagnosis. Tissue was analyzed for 138 patients. Targeted sequencing resulted in diagnostically significant alterations in 80 of 138 (57%) of patients and therapeutically significant alterations in 58 of 138 (42%) patients. To date, 18 patients in our cohort have been treated with medical therapy informed by their genetic diagnosis. Several more await enrollment on clinical trials. For patients with diagnoses previously categorized as unknown (n=11), sequencing led to identification of a genetic variant in 6 patients (54%). Additionally, 8/138 patients had variants requiring further evaluation for potential germline involvement. Discussion: Next generation sequencing in vascular anomalies patients identified actionable variants in a large proportion of the patients in our cohort. The mTOR inhibitor sirolimus has been used to treat a variety of vascular anomalies, but not all patients respond to this treatment. Targeted therapies based on specific genotypes hold promise as clinical trials in vascular anomalies are emerging. Additionally, sequencing in this cohort identified several variants suggesting a germline cancer predisposition requiring follow-up. Use of next generation sequencing has clinical utility and increased use of this testing may improve diagnosis, prognosis, and treatment for patients with vascular anomalies. Disclosures Adams: Novartis: Consultancy; Venthura: Consultancy. OffLabel Disclosure: Sirolimus is used off-label for the treatment of vascular anomalies.

scholarly journals Targeted next-generation sequencing for the genetic diagnosis of dysferlinopathy

2015 ◽  
Vol 357 ◽  
pp. e345
Author(s):  
H. Shin ◽  
H. Jang ◽  
H. Park ◽  
J. Lee ◽  
S. Kim ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Diagnosis ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

Targeted next generation sequencing for genetic diagnosis of familial hypercholesterolemia

2014 ◽  
Vol 235 (2) ◽  
pp. e100
Author(s):  
C. Maglio ◽  
R.M. Mancina ◽  
B.M. Motta ◽  
C. Pirazzi ◽  
O. Wiklund ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Familial Hypercholesterolemia ◽  
Genetic Diagnosis ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing
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