scholarly journals A.07 Genomics of atypical dyskinetic cerebral palsy – opportunities for improved diagnosis and management

2017 ◽  
Vol 44 (S2) ◽  
pp. S10-S10
Author(s):  
H Goez ◽  
A Matthews ◽  
B Al Jabri ◽  
I Blydt-Hansen ◽  
J Andersen ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Inborn Errors Of Metabolism ◽  
Inborn Errors ◽  
Chromosomal Disorders ◽  
Glutaric Aciduria ◽  
Whole Exome ◽  
Deep Brain

Background: Cerebral palsy (CP) is a debilitating disorder (1). Based on neuromotor impairments it is divided to spastic, dyskinetic and ataxic types (2). Inborn Errors of Metabolism (IEMs), monogenic and chromosomal disorders mimic CP (3). We aimed to identify causal genetic variants in patients with atypical dyskinetic CP in whom known IEMs were ruled out. Timely diagnosis is essential for proper management, especially in conditions that mimic CP and are treatable. Methods: We enrolled 23 patients with unexplained atypical dyskinetic CP, for whole exome sequencing. Variants were filtered against public and in-house databases to identify variants predicted as damaging (in silico tools and ACMG criteria). We applied a virtual gene panel of known and suspected CP and movement disorder genes and investigated each sample. Results: The participants presented with symptoms including: spasticity, dystonia, choera-athetosis, ataxia and cognitive delays. We identified 23 diagnoses: 13 dominant,6 recessive and 4 X-linked. 12 patients had movement disorders. In 4, the diagnoses enabled targeted treatment (neurotransmitter supplements in Unverricht Lundborg diseases (CSTB) and PAK3 deficiency, deep brain stimulation in GNAO1 deficiency, medical diet in Glutaric Aciduria (GCDH). Conclusions: Whole Exome Sequencing contributes to establishing diagnosis in patients with atypical dyskinetic CP resulting in precision medicine and improved health outcomes.

scholarly journals Analysis workflow to assess de novo genetic variants from human whole-exome sequencing

2021 ◽  
Vol 2 (1) ◽  
pp. 100383
Author(s):  
Nicholas S. Diab ◽  
Spencer King ◽  
Weilai Dong ◽  
Garrett Allington ◽  
Amar Sheth ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
De Novo ◽  
Whole Exome ◽  
Analysis Workflow

scholarly journals Identification of rare genetic variants in Juvenile Idiopathic Arthritis using whole exome sequencing

2015 ◽  
Vol 13 (S1) ◽  
Author(s):  
E Sanchez ◽  
S Grandemange ◽  
F Tran Mau-Them ◽  
P Louis-Plence ◽  
A Carbasse ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Whole Exome ◽  
Rare Genetic Variants

Whole-Exome Sequencing-Based Approach for Germline Mutations in Patients with Inborn Errors of Immunity

2020 ◽  
Vol 40 (5) ◽  
pp. 729-740 ◽  
Author(s):  
Tsubasa Okano ◽  
Kohsuke Imai ◽  
Takuya Naruto ◽  
Satoshi Okada ◽  
Motoi Yamashita ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Germline Mutations ◽  
Inborn Errors ◽  
Inborn Errors Of Immunity ◽  
Whole Exome

scholarly journals Whole-exome sequencing points to considerable genetic heterogeneity of cerebral palsy

2015 ◽  
Vol 20 (2) ◽  
pp. 176-182 ◽  
Author(s):  
G McMichael ◽  
M N Bainbridge ◽  
E Haan ◽  
M Corbett ◽  
A Gardner ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Heterogeneity ◽  
Whole Exome

scholarly journals Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

Haematologica ◽  
2016 ◽  
Vol 101 (10) ◽  
pp. 1170-1179 ◽  
Author(s):  
B. Johnson ◽  
G. C. Lowe ◽  
J. Futterer ◽  
M. Lordkipanidze ◽  
D. MacDonald ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Whole Exome ◽  
Inherited Thrombocytopenia

scholarly journals Comprehensive genetic analysis by whole exome sequencing in 352 Korean pediatric patients with unknown neurodevelopmental disorders

2018 ◽  
Author(s):  
Youngha Lee ◽  
Jin Sook Lee ◽  
Soo Yeon Kim ◽  
Jaeso Cho ◽  
Yongjin Yoo ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Neurodevelopmental Disorders ◽  
Pediatric Patients ◽  
Medical System ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Novel Variants

AbstractImportanceAccurate diagnosis of pediatric patients with complicated neurological problems demands a well-coordinated combination of robust genetic analytic capability and delicate clinical evaluation. It should be tested whether this challenge can be augmented by whole exome sequencing (WES).ObjectiveTo evaluate the utility of WES-based diagnosis and discovery of novel variants of undiagnosed patients with complex neurodevelopmental problems in a country with a centralized medical system.Design, setting, and participantsA cohort of 352 Korean patients, believed to cover a major portion of the entire country from July 2014 to April 2017, with a broad spectrum of neurodevelopmental disorders without any pathogenic variants revealed by conventional methods were evaluated by trio-based WES at Seoul National University Children’s Hospital.ExposuresWES of patients and parents and subsequent evaluation of genetic variants.Main outcomes and measuresGenetic variants from each patient were evaluated for known disease association and novel variants were assessed for possible involvement with neurodevelopment process.ResultsWe identified disease-causing variants, including newly discovered variants, in 57.4% of the probands, who had underwent a mean of 5.6 years of undiagnosed periods and visited mean of 2.3 tertiary hospitals. The cohort included 112 patients with variants that were previously reported as pathogenic (31.8%), 16 patients with copy number variants (4.5%) and 27 patients with variants that were associated with different clinical symptoms (7.7%). We also discovered potentially pathogenic variants from 47 patients that required further functional assessments (13.4%) and demonstrated potential implications in neurodevelopmental disorders. Following the genetic analysis, we provided more precise treatments to selected patients. A few clinical vignettes are presented that illuminate the potential diagnostic pitfalls that one could have encountered without this approach.Conclusions and relevanceOur results highlight the utility of WES-based diagnosis for improved patient care in a country with a centralized medical system and discovery of novel pathophysiology mechanisms.Key pointsQuestionWhat is the advantage of whole exome sequencing based diagnosis of pediatric neurology patients with unknown rare symptoms in a large tertiary clinic in a country with a centralized medical system?FindingsWhole exome sequencing of 352 Korean patients, with a mean of 5.7 years of undiagnosed period, yielded 44.0% of conservative diagnostic yield. A number of cases were directly benefitted by trio-based WES via termination of diagnostic odyssey, genetic counseling for next offspring, or suggestion of more effective and customized treatment options.MeaningWe report on the establishment of a national-level whole exome-based diagnosis system, with emphasis on deliberate integration of clinical interpretation and genetic analysis. Whole exome sequencing should be a choice of diagnostic tools for pediatric neurologic patients with ambiguous symptoms.

Identification of novel and rare recurrent genetic variants in early onset chronic pancreatitis by whole exome sequencing

Pancreatology ◽  
2019 ◽  
Vol 19 ◽  
pp. S20
Author(s):  
Agnieszka Rygiel ◽  
Grzegorz Oracz ◽  
Tomasz Gambin ◽  
Elwira Kołodziejczyk ◽  
Joanna Kosinska ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Early Onset ◽  
Whole Exome
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