Molecular diagnosis of primary hypertriglyceridemias by next generation sequencing (NGS): Preliminary results and open questions

2017 ◽  
Vol 27 (1) ◽  
pp. e33-e34
Author(s):  
C. Rabacchi ◽  
E. Tenedini ◽  
I. Bernardis ◽  
M.L. Simone ◽  
E. Tagliafico ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Molecular Diagnosis ◽  
Next Generation ◽  
Preliminary Results ◽  
Open Questions ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

scholarly journals Next-generation sequencing approach to hyperCKemia

2019 ◽  
Vol 5 (5) ◽  
pp. e352 ◽  
Author(s):  
Anna Rubegni ◽  
Alessandro Malandrini ◽  
Claudia Dosi ◽  
Guja Astrea ◽  
Jacopo Baldacci ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Molecular Diagnosis ◽  
Diagnostic Yield ◽  
Clinical Neurology ◽  
Next Generation ◽  
Variants Of Unknown Significance ◽  
Unknown Significance ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

ObjectiveNext-generation sequencing (NGS) was applied in molecularly undiagnosed asymptomatic or paucisymptomatic hyperCKemia to investigate whether this technique might allow detection of the genetic basis of the condition.MethodsSixty-six patients with undiagnosed asymptomatic or paucisymptomatic hyperCKemia, referred to tertiary neuromuscular centers over an approximately 2-year period, were analyzed using a customized, targeted sequencing panel able to investigate the coding exons and flanking intronic regions of 78 genes associated with limb-girdle muscular dystrophies, rhabdomyolysis, and metabolic and distal myopathies.ResultsA molecular diagnosis was reached in 33 cases, corresponding to a positive diagnostic yield of 50%. Variants of unknown significance were found in 17 patients (26%), whereas 16 cases (24%) remained molecularly undefined. The major features of the diagnosed cases were mild proximal muscle weakness (found in 27%) and myalgia (in 24%). Fourteen patients with a molecular diagnosis and mild myopathic features on muscle biopsy remained asymptomatic at a 24-month follow-up.ConclusionsThis study of patients with undiagnosed hyperCKemia, highlighting the advantages of NGS used as a first-tier diagnostic approach in genetically heterogeneous conditions, illustrates the ongoing evolution of molecular diagnosis in the field of clinical neurology. Isolated hyperCKemia can be the sole feature alerting to a progressive muscular disorder requiring careful surveillance.

scholarly journals Next-Generation Sequencing-Based Molecular Diagnosis of Choroideremia

2015 ◽  
Vol 6 (2) ◽  
pp. 246-250 ◽  
Author(s):  
Kayo Shimizu ◽  
Akio Oishi ◽  
Maho Oishi ◽  
Ken Ogino ◽  
Satoshi Morooka ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Retinal Detachment ◽  
Macular Hole ◽  
Molecular Diagnosis ◽  
Novel Mutation ◽  
Case Series ◽  
Next Generation ◽  
Macular Hole Retinal Detachment ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

We screened patients with choroideremia using next-generation sequencing (NGS) and identified a novel mutation and a known mutation in the CHM gene. One patient presented an atypical fundus appearance for choroideremia. Another patient presented macular hole retinal detachment in the left eye. The present case series shows the utility of NGS-based screening in patients with choroideremia. In addition, the presence of macular hole in 1 of the 2 patients, together with a previous report, indicated the susceptibility of patients with choroideremia to macular hole.

Improved molecular diagnosis of patients with neonatal diabetes using a combined next-generation sequencing and MS-MLPA approach

2016 ◽  
Vol 29 (5) ◽  
Author(s):  
Gorka Alkorta-Aranburu ◽  
Madina Sukhanova ◽  
David Carmody ◽  
Trevor Hoffman ◽  
Latrice Wysinger ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Molecular Diagnosis ◽  
Neonatal Diabetes ◽  
Unknown Etiology ◽  
Chromosome 6 ◽  
Next Generation ◽  
Transient Neonatal Diabetes ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Parental Inheritance

Abstract: We evaluated a methylation-specific multiplex-ligation-dependent probe amplification (MS-MLPA) assay for the molecular diagnosis of transient neonatal diabetes mellitus (TNDM) caused by 6q24 abnormalities and assessed the clinical utility of using this assay in combination with next generation sequencing (NGS) analysis for diagnosing patients with neonatal diabetes (NDM).: We performed MS-MLPA in 18 control samples and 42 retrospective NDM cases with normal bi-parental inheritance of chromosome 6. Next, we evaluated 22 prospective patients by combining NGS analysis of 11 NDM genes and the MS-MLPA assay.: 6q24 aberrations were identified in all controls and in 19% of patients with normal bi-parental inheritance of chromosome 6. The MS-MLPA/NGS combined approach identified a genetic cause in ~64% of patients with NDM of unknown etiology.MS-MLPA is a reliable method to identify all known 6q24 abnormalities and comprehensive testing of all causes reveals a causal mutation in ~64% of patients.

scholarly journals Unravelling the Complexity of Inherited Retinal Dystrophies Molecular Testing: Added Value of Targeted Next-Generation Sequencing

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Isabella Bernardis ◽  
Laura Chiesi ◽  
Elena Tenedini ◽  
Lucia Artuso ◽  
Antonio Percesepe ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Molecular Diagnosis ◽  
Genetic Alterations ◽  
Macular Dystrophy ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

To assess the clinical utility of targeted Next-Generation Sequencing (NGS) for the diagnosis of Inherited Retinal Dystrophies (IRDs), a total of 109 subjects were enrolled in the study, including 88 IRD affected probands and 21 healthy relatives. Clinical diagnoses included Retinitis Pigmentosa (RP), Leber Congenital Amaurosis (LCA), Stargardt Disease (STGD), Best Macular Dystrophy (BMD), Usher Syndrome (USH), and other IRDs with undefined clinical diagnosis. Participants underwent a complete ophthalmologic examination followed by genetic counseling. A custom AmpliSeq™ panel of 72 IRD-related genes was designed for the analysis and tested using Ion semiconductor Next-Generation Sequencing (NGS). Potential disease-causing mutations were identified in 59.1% of probands, comprising mutations in 16 genes. The highest diagnostic yields were achieved for BMD, LCA, USH, and STGD patients, whereas RP confirmed its high genetic heterogeneity. Causative mutations were identified in 17.6% of probands with undefined diagnosis. Revision of the initial diagnosis was performed for 9.6% of genetically diagnosed patients. This study demonstrates that NGS represents a comprehensive cost-effective approach for IRDs molecular diagnosis. The identification of the genetic alterations underlying the phenotype enabled the clinicians to achieve a more accurate diagnosis. The results emphasize the importance of molecular diagnosis coupled with clinic information to unravel the extensive phenotypic heterogeneity of these diseases.

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