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.

In silico prediction of the pathogenic effect of a novel variant of BCKDHA leading to classical maple syrup urine disease identified using clinical exome sequencing

2018 ◽  
Vol 483 ◽  
pp. 33-38
Author(s):  
Cynthia Fernández-Lainez ◽  
Carmen Aláez-Verson ◽  
Isabel Ibarra-González ◽  
Sergio Enríquez-Flores ◽  
Karol Carrillo-Sanchez ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Maple Syrup Urine Disease ◽  
In Silico ◽  
In Silico Prediction ◽  
Maple Syrup ◽  
Clinical Exome Sequencing ◽  
Pathogenic Effect ◽  
Novel Variant ◽  
Urine Disease

Voltage-gated potassium channel limbic encephalitis presenting as functional cognitive impairment

2020 ◽  
Vol 13 (12) ◽  
pp. e233179
Author(s):  
Eric Garrels ◽  
Fawziya Huq ◽  
Gavin McKay
Keyword(s):  
Cognitive Impairment ◽  
Case Report ◽  
Potassium Channel ◽  
Limbic Encephalitis ◽  
Psychiatric Symptoms ◽  
Differential Diagnoses ◽  
Visual Hallucinations ◽  
Voltage Gated ◽  
History Of ◽  
Impaired Cognition

Limbic encephalitis is often reported to present as seizures and impaired cognition with little focus on psychiatric presentations. In this case report, we present a 49-year-old man who initially presented to the Psychiatric Liaison Service with a several month history of confusion with the additional emergence of visual hallucinations and delusions. Due to the inconsistent nature of the symptoms in the context of a major financial stressor, a provisional functional cognitive impairment diagnosis was made. Investigations later revealed a positive titre of voltage-gated potassium channel (VGKC) antibodies, subtype leucine-rich glioma inactivated 1 accounting for his symptoms which dramatically resolved with steroids and immunoglobulins. This case highlighted the need for maintaining broad differential diagnoses in a patient presenting with unusual psychiatric symptoms.

scholarly journals Novel SCN5A p.Val1667Asp Missense Variant Segregation and Characterization in a Family with Severe Brugada Syndrome and Multiple Sudden Deaths

2021 ◽  
Vol 22 (9) ◽  
pp. 4700
Author(s):  
Michelle M. Monasky ◽  
Emanuele Micaglio ◽  
Giuseppe Ciconte ◽  
Ilaria Rivolta ◽  
Valeria Borrelli ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Risk Stratification ◽  
Brugada Syndrome ◽  
Electrophysiological Study ◽  
Functional Characterization ◽  
The Family ◽  
Novel Variant ◽  
History Of ◽  
Scn5a Gene

Genetic testing in Brugada syndrome (BrS) is still not considered to be useful for clinical management of patients in the majority of cases, due to the current lack of understanding about the effect of specific variants. Additionally, family history of sudden death is generally not considered useful for arrhythmic risk stratification. We sought to demonstrate the usefulness of genetic testing and family history in diagnosis and risk stratification. The family history was collected for a proband who presented with a personal history of aborted cardiac arrest and in whom a novel variant in the SCN5A gene was found. Living family members underwent ajmaline testing, electrophysiological study, and genetic testing to determine genotype-phenotype segregation, if any. Patch-clamp experiments on transfected human embryonic kidney 293 cells enabled the functional characterization of the SCN5A novel variant in vitro. In this study, we provide crucial human data on the novel heterozygous variant NM_198056.2:c.5000T>A (p.Val1667Asp) in the SCN5A gene, and demonstrate its segregation with a severe form of BrS and multiple sudden deaths. Functional data revealed a loss of function of the protein affected by the variant. These results provide the first disease association with this variant and demonstrate the usefulness of genetic testing for diagnosis and risk stratification in certain patients. This study also demonstrates the usefulness of collecting the family history, which can assist in understanding the severity of the disease in certain situations and confirm the importance of the functional studies to distinguish between pathogenic mutations and harmless genetic variants.

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

scholarly journals 451. Evaluation of Exposure History in Healthcare Personnel with Coronavirus 2019 Disease

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S293-S293
Author(s):  
Sandra Silva ◽  
Thriveen Mana ◽  
Davinder Bhullar ◽  
Beatrice Tabor ◽  
Curtis Donskey
Keyword(s):  
High Risk ◽  
Risk Exposure ◽  
Healthcare Personnel ◽  
Administrative Personnel ◽  
Asymptomatic Carriage ◽  
Moderate Disease ◽  
Control And Prevention ◽  
History Of ◽  
Exposure History ◽  
Atypical Presentations

Abstract Background During the Coronavirus Disease 2019 (COVID-19) pandemic, many healthcare personnel (HCP) have developed COVID-19. However, there is uncertainty regarding whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was acquired at work versus in the community. Methods We conducted a cohort study to examine exposure history of personnel with COVID-19 infection or asymptomatic carriage in a VA healthcare system. High-risk exposures were classified based Centers for Disease Control and Prevention criteria. Results Of 578 personnel tested, 49 (8%) had nasopharyngeal swabs with positive PCR results, including 45 (92%) with and 4 (8%) without COVID-19 symptoms. Of the 49 cases, 21 (43%) had a documented high-risk exposure at work, including 14 exposures to COVID-19 patients and 7 exposures to colonized or infected personnel. Exposures to infected patients most often were a result of delays in recognition of COVID-19 due to atypical presentations. Exposures to personnel with COVID-19 most often involved activities such as meals when facemasks were not worn. Most cases occurred among nurses (26, 53%) and administrative personnel (10, 20%); only 3 physicians developed COVID-19. No cases occurred in personnel working on COVID-19 wards. All personnel had mild or moderate disease. Conclusion Forty-three percent of healthcare personnel with COVID-19 had prior high-risk exposures at work. Improved detection of patients with atypical presentations and efforts to reduce high-risk contacts among personnel may reduce the risk for acquisition of SARS-CoV-2. Disclosures All Authors: No reported disclosures

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 335 - BEHÇET DISEASE PRESENTING WITH ACUTE PSYCHOSIS

2020 ◽  
Vol 32 (S1) ◽  
pp. 94-94
Author(s):  
A.M. Carvalheiro ◽  
A.R. Fonseca ◽  
J. Maia
Keyword(s):  
Psychiatric Symptoms ◽  
Retinal Vasculitis ◽  
Posterior Uveitis ◽  
Neurological Involvement ◽  
Behçet Disease ◽  
Acute Psychosis ◽  
Behcet Disease ◽  
Persecutory Delusions ◽  
Starting Point ◽  
History Of

ObjectivesUsing as a starting point a clinical case, the authors performed a literature review to clarify the relationship between Behçet disease and acute psychosis.MethodsAnalysis of the patient's clinical process and brief review of the latest available literature on the subject, published in PubMed/Medline databases.ResultsMale patient, 55 years old, brought to the emergency room by fever, headache, hetero-aggressive behavior, disinhibited behavior, mood swings, euphoria, persecutory delusions and insomnia, in the last 4 days. He had no insight into his illness. There was no personal or family history of psychiatric illness and toxicological habits were irrelevant. Due to the personal history of posterior uveitis with bilateral macular edema, retinal vasculitis, genital aphthosis, papulo-vesicular lesions and recurrent bipolar aphthosis, the hypothesis of neuro-behçet was raised.ConclusionsBehçet's disease can present with neurological involvement - neuro -behçet - and can manifest itself with several psychiatric symptoms (euphoria, lack of insight, disinhibited behavior, agitation or psychomotor retardation, persecutory delusions, obsessive thoughts, anxiety, depression, insomnia or memory changes). Fever and headache usually appear in the prodromal stage and can be signs of onset or recurrence of the disease. The prevalence of neuro-behçet ranges from 2 to 50% and usually occurs 1 to 10 years after the first symptoms of the disease. Since it appears as the first manifestation of the disease in only 3% of cases, it is difficult to diagnose. The literature suggests that symptoms are generally resistant to treatment with conventional psychotropic drugs and so it is an important cause of morbidity and mortality.”

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