Utility of clinical exome sequencing in progressive myoclonus epilepsy syndromes: An exploratory analysis

2021 ◽  
Author(s):  
Manna Jose ◽  
Prashant Poulose ◽  
Soumya Sundaram ◽  
Ashalatha Radhakrishnan ◽  
Sheela Nampoothiri ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Exploratory Analysis ◽  
Progressive Myoclonus Epilepsy ◽  
Clinical Exome Sequencing ◽  
Myoclonus Epilepsy

scholarly journals Linkage analysis and exome sequencing identify a novel mutation inKCTD7in patients with progressive myoclonus epilepsy with ataxia

Epilepsia ◽  
2014 ◽  
Vol 55 (9) ◽  
pp. e106-e111 ◽  
Author(s):  
Sali M. K. Farhan ◽  
Lisa M. Murphy ◽  
John F. Robinson ◽  
Jian Wang ◽  
Victoria M. Siu ◽  
...  
Keyword(s):  
Linkage Analysis ◽  
Exome Sequencing ◽  
Novel Mutation ◽  
Progressive Myoclonus Epilepsy ◽  
Myoclonus Epilepsy

An audit and insights from clinical exome sequencing in psychiatry: genotype-phenotype correlation

2020 ◽  
Author(s):  
Jayant Mahadevan ◽  
Reeteka Sud ◽  
Ravi Kumar Nadella ◽  
Vani P ◽  
Anand G Subramaniam ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Psychiatric Symptoms ◽  
Pathogenic Variant ◽  
Clinical Exome Sequencing ◽  
Mapt Gene ◽  
Nf1 Gene ◽  
Novel Variant ◽  
History Of ◽  
Atypical Presentations ◽  
Minor Physical Anomalies

BACKGROUND:Psychiatric syndromes have polymorphic symptomatology, and are known to be heritable. Psychiatric symptoms (and even syndromes) often occur as part of the clinical presentation in rare Mendelian syndromes. Clinical exome sequencing reports may help with refining diagnosis and influence treatment decisions, in addition to providing a window into the biology of brain and behaviour. We describe a clinical audit of 12 individuals who sought treatment at our hospital, and for whom targeted sequencing was ordered. Three cases are discussed in detail to demonstrate correlations between genotype and phenotype in the clinic.METHODS:Targeted Next-Generation Sequencing (NGS) was done using Clinical Exome Panel (TruSight One, Illumina) covering coding exons and flanking intronic sequences of 4811 genes associated with known inherited diseases. Variants detected were classified according to the American College for Medical Genetics (ACMG) recommendation for standards of interpretation and reporting of sequence variations.RESULTS:Ten out of twelve cases had at least one pathogenic variant. In one of these cases, we detected a known pathogenic variant in MAPT gene in a suspected FTD case, which helped us to confirm the diagnosis. In another case, we detected a novel variant predicted to be deleterious in NF1 gene. Identification of this mutation suggested a change in treatment for the patient, that was of benefit. The same patient also harboured a novel variant in the TRIO gene. This gene may be involved in biological processes that underlie the patient’s psychiatric illness.CONCLUSIONS:The cases discussed here exemplify different scenarios under which targeted exome sequencing can find meaningful application in the clinic: confirming diagnosis (MAPT variant), or modifying treatment (NF1). We suggest that clinical exome sequencing can be a helpful addition to a clinician’s toolkit when there are expediting factors to consider— such as early-onset, strong family history of mental illness, complex/atypical presentations and minor physical anomalies or neurocutaneous markers.

scholarly journals Genetic landscape of recessive diseases in the Vietnamese population from large‐scale clinical exome sequencing

2021 ◽  
Author(s):  
Ngoc Hieu Tran ◽  
Thanh‐Huong Nguyen Thi ◽  
Hung‐Sang Tang ◽  
Le‐Phuc Hoang ◽  
Trung‐Hieu Le Nguyen ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Large Scale ◽  
Clinical Exome Sequencing ◽  
Genetic Landscape ◽  
Vietnamese Population

Fetal pulmonary choristoma: report of first case and literature review

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Anupam Nanda ◽  
Rajinder Nanda ◽  
Seema Thakur ◽  
Tej Prakash Gupta ◽  
Sudhir Jain ◽  
...  
Keyword(s):  
Literature Review ◽  
Exome Sequencing ◽  
Posterior Fossa ◽  
Spinal Column ◽  
Fetal Autopsy ◽  
Case Presentation ◽  
Antenatal Ultrasound ◽  
Clinical Exome Sequencing ◽  
First Case ◽  
Pathologic Findings

AbstractObjectivesLung tissue choristoma is a very rare disorder where mature lung tissues develop in the site not normal to the lung.Case presentationWe hereby report a first case of fetal pulmonary choristoma in a 23–24 weeks fetus where antenatal ultrasound showed a mass in posterior fossa with severe ventriculomegaly. The mass extended inferiorly in cervical spinal column and thereafter extended in the skin over the back of fetus. Fetal autopsy confirmed these findings. Pathologic findings showed mature lung tissues with bronchi, bronchioles, and alveoli. Clinical exome sequencing showed normal results.ConclusionsWe describe the antenatal ultrasound, fetal autopsy and pathologic findings of an intracranial and cutaneous pulmonary choristoma.

scholarly journals Altered Expression of Peroxiredoxins in Mouse Model of Progressive Myoclonus Epilepsy upon LPS-Induced Neuroinflammation

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 357
Author(s):  
Mojca Trstenjak Prebanda ◽  
Petra Matjan-Štefin ◽  
Boris Turk ◽  
Nataša Kopitar-Jerala
Keyword(s):  
Mouse Model ◽  
Redox Homeostasis ◽  
Underlying Mechanism ◽  
Loss Of Function ◽  
Altered Expression ◽  
Lps Challenge ◽  
Progressive Myoclonus Epilepsy ◽  
Myoclonus Epilepsy ◽  
The Brain ◽  
Deficient Mice

Stefin B (cystatin B) is an inhibitor of endo-lysosomal cysteine cathepsin, and the loss-of-function mutations in the stefin B gene were reported in patients with Unverricht–Lundborg disease (EPM1), a form of progressive myoclonus epilepsy. Stefin B-deficient mice, a mouse model of the disease, display key features of EPM1, including myoclonic seizures. Although the underlying mechanism is not yet completely clear, it was reported that the impaired redox homeostasis and inflammation in the brain contribute to the progression of the disease. In the present study, we investigated if lipopolysaccharide (LPS)-triggered neuroinflammation affected the protein levels of redox-sensitive proteins: thioredoxin (Trx1), thioredoxin reductase (TrxR), peroxiredoxins (Prxs) in brain and cerebella of stefin B-deficient mice. LPS challenge was found to result in a marked elevation of Trx1 and TrxR in the brain and cerebella of stefin B deficient mice, while Prx1 was upregulated only in cerebella after LPS challenge. Mitochondrial peroxiredoxin 3 (Prx3), was upregulated also in the cerebellar tissue lysates prepared from unchallenged stefin B deficient mice, while after LPS challenge Prx3 was upregulated in stefin B deficient brain and cerebella. Our results imply the role of oxidative stress in the progression of the disease.

scholarly journals Accurate Molecular Diagnosis of Gaucher Disease Using Clinical Exome Sequencing as a First-Tier Test

2021 ◽  
Vol 22 (11) ◽  
pp. 5538
Author(s):  
Stefania Zampieri ◽  
Silvia Cattarossi ◽  
Eleonora Pavan ◽  
Antonio Barbato ◽  
Agata Fiumara ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Molecular Diagnosis ◽  
Gaucher Disease ◽  
Novel Mutation ◽  
Large Deletion ◽  
Clinical Exome Sequencing ◽  
Number Variation ◽  
Long Range Pcr ◽  
Set Up ◽  
Beta Glucosidase

Gaucher disease (GD) is an autosomal recessive lysosomal disorder due to beta-glucosidase gene (GBA) mutations. The molecular diagnosis of GD is complicated by the presence of recombinant alleles originating from a highly homologous pseudogene. Clinical exome sequencing (CES) is a rapid genetic approach for identifying disease-causing mutations. However, copy number variation and recombination events are poorly detected, and further investigations are required to avoid mis-genotyping. The aim of this work was to set-up an integrated strategy for GD patients genotyping using CES as a first-line test. Eight patients diagnosed with GD were analyzed by CES. Five patients were fully genotyped, while three were revealed to be homozygous for mutations that were not confirmed in the parents. Therefore, MLPA (multiplex ligation-dependent probe amplification) and specific long-range PCR were performed, and two recombinant alleles, one of them novel, and one large deletion were identified. Furthermore, an MLPA assay performed in one family resulted in the identification of an additional novel mutation (p.M124V) in a relative, in trans with the known p.N409S mutation. In conclusion, even though CES has become extensively used in clinical practice, our study emphasizes the importance of a comprehensive molecular strategy to provide proper GBA genotyping and genetic counseling.

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