A Novel Mutation in ATP7B Gene Associated with Severe Neurological and Psychiatric Symptoms

Wilson disease (WD) (OMIM# 277900) is an autosomal recessive inherited disorder characterized by excess copper (Cu) storage in different human tissues, such as the brain, liver, and the corneas of the eyes. It is a rare disorder that occurs in approximately 1 in 30,000 individuals. The clinical presentations of WD are highly varied, primarily consisting of hepatic and neurological conditions. WD is caused by homozygous or compound heterozygous mutations in the ATP7B gene. The diagnosis of the disease is complicated because of its heterogeneous phenotypes. The molecular genetic analysis encourages early diagnosis, treatment, and the opportunity to screen individuals at risk in the family. In this paper, we reported a case with a novel, hotspot-located mutation in WD. We have suggested that this mutation in the ATP7B gene might contribute to liver findings, progressing to liver failure with a loss of function effect. Besides this, if patients have liver symptoms in childhood and/or are children of consanguineous parents, WD should be considered during the evaluation of the patients.

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Spectrum of ATP7B Gene Mutations in Pakistani Wilson Disease Patients: A Novel Mutation Is Associated with Severe Hepatic and Neurological Complication

International Journal of Biology ◽

10.5539/ijb.v2n1p117 ◽

2010 ◽

Vol 2 (1) ◽

Cited By ~ 1

Author(s):

Abdul Khaliq Naveed ◽

Asifa Majeed ◽

Sumreena Mansoor

Keyword(s):

Wilson Disease ◽

Novel Mutation ◽

Neurological Complication ◽

Gene Mutations ◽

Atp7b Gene

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New novel mutation of the ATP7B gene in a family with Wilson disease

Journal of the Neurological Sciences ◽

10.1016/j.jns.2011.09.007 ◽

2012 ◽

Vol 313 (1-2) ◽

pp. 129-131 ◽

Cited By ~ 2

Author(s):

Jun-Young Lee ◽

Young-Hyun Kim ◽

Tae-Woo Kim ◽

Sun-Young Oh ◽

Dal-Sik Kim ◽

...

Keyword(s):

Wilson Disease ◽

Novel Mutation ◽

Atp7b Gene ◽

New Novel

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Allele Dropout in PCR-Based Diagnosis of Wilson Disease: Mechanisms and Solutions

Clinical Chemistry ◽

10.1373/clinchem.2005.060491 ◽

2006 ◽

Vol 52 (3) ◽

pp. 517-520 ◽

Cited By ~ 23

Author(s):

Ching-Wan Lam ◽

Chloe M Mak

Keyword(s):

Wilson Disease ◽

Chinese Population ◽

Novel Mutation ◽

Hong Kong Chinese ◽

Atp7b Gene ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Direct Dna Sequencing ◽

Allele Dropout ◽

Disease Mechanisms

Abstract Background: We investigated the mechanisms leading to allele dropout—the nonamplification of 1 of the alleles—in PCR-based diagnosis of Wilson disease (WD). Methods: We extracted genomic DNA from blood samples from 6 WD patients (P1–P6) with allele dropouts detected in a previous study of WD in a Hong Kong Chinese population. We amplified the ATP7B gene by PCR and performed direct DNA sequencing of all exons of the ATP7B gene. To support the proposed mechanism of allele dropout, we used proofreading DNA polymerase, primer design avoiding single-nucleotide polymorphism sites, and duplex PCR. Results: Patients P1–P4 were all apparently homozygous for a known disease-causing mutation, c.2975C>T (p.P992L) in exon 13. Patient P5 was apparently homozygous for a novel mutation, c.2524G>A, and patient P6 was apparently homozygous for another known mutation, c.522_523insA (p.K175K-fs). In all cases, we determined that the patients were actually heterozygous for these mutations. Conclusion: Our results confirm that allele dropout is the mechanism causing apparent homozygosity of heterozygous mutations in these WD patients.

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Case Report: A Novel GNB1 Mutation Causes Global Developmental Delay With Intellectual Disability and Behavioral Disorders

Frontiers in Neurology ◽

10.3389/fneur.2021.735549 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jorge Diogo Da Silva ◽

Marta Daniela Costa ◽

Bruno Almeida ◽

Fátima Lopes ◽

Patrícia Maciel ◽

...

Keyword(s):

Intellectual Disability ◽

Developmental Delay ◽

Behavioral Disorders ◽

Psychiatric Symptoms ◽

Novel Mutation ◽

Autism Spectrum ◽

Global Developmental Delay ◽

Missense Mutations ◽

Protein Subunit ◽

Neurodevelopmental Disease

Diseases of neurodevelopment mostly exhibit neurological and psychiatric symptoms that go from very mild to extremely severe. While the etiology of most cases of neurodevelopmental disease is still unknown, the discovery of underlying genetic causes is rapidly increasing, with hundreds of genes being currently implicated as disease-causing. Here, we report a clinical case of a patient with a previously undiagnosed syndrome comprising severe global developmental delay, intellectual disability, and behavioral disorders (such as attention-deficit/hyperactivity disorder, autism spectrum disorder and recurrent bouts of aggressive behavior). After genetic testing, a pathogenic variant was detected in the GNB1 gene, which codes for the G-protein subunit β1. The detected variant (c.217G>A, p.A73T) has not been previously reported in any of the 58 published cases of GNB1 encephalopathy. However, it localizes to the mutational hotspot in exons 6 and 7 in which 88% of all missense mutations occur. An in silico model predicts that this mutation is likely to disrupt the WD40 domain of the GNB1 protein, which is required for its interaction with other G-proteins and, consequently, for downstream signal transduction. In conclusion, we reported an additional GNB1 encephalopathy patient, bearing a novel mutation, taking another step toward a better understanding of its clinical presentation and prospective development of treatments for the disease.

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Wilson’s Disease in Children : An Update

Z H Sikder Women’s Medical College Journal ◽

10.47648/zhswmcj.2020.v0201.07 ◽

2020 ◽

Vol 2 (Number 1) ◽

pp. 27-30

Author(s):

Sadika Kadir ◽

Tamanna Begum ◽

Mohammed Ashraful Haque ◽

Nirupama Najim ◽

Shayma Chakravarty ◽

...

Keyword(s):

Liver Failure ◽

Acute Liver Failure ◽

Wilson’S Disease ◽

Psychiatric Symptoms ◽

Copper Metabolism ◽

Autosomal Recessive Disorder ◽

Wilson's Disease ◽

Atp7b Gene ◽

Biochemical Tests ◽

Serum Ceruloplasmin

Wilson’s Disease is an autosomal recessive disorder of copper metabolism due to ATP7B gene defect. This defect result in progressive toxic accumulation of copper in liver, CNS, cornea, skeletal system and other organs. Clinical presentations of Wilson’s disease (WD) in childhood ranges from asymptomatic liver disease to cirrhosis or acute liver failure, whereas neurological and psychiatric symptoms are rare. The basic diagnostic approach includes serum ceruloplasmin and 24-hour urinary copper excretion. Final diagnosis of WD can be established using a diagnostic scoring system based on symptoms, biochemical tests assessing copper metabolism, and molecular analysis of mutations in the ATP7B gene. Pharmacological treatment is life-long and aims at removal of copper excess by chelating agents as D-penicillamine, trientine or inhibition of intestinal copper absorption with zinc salts. Acute liver failure often requires liver transplantation. Genetic therapy and haplocyte transplantation represent future curative treatment for Wilson’s disease.

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Psychiatric Onset Alexander Disease: An Important Challenge in Neuropsychiatric Diagnosis

Basic and Clinical Neuroscience Journal ◽

10.32598/bcn.2021.1551.1 ◽

2021 ◽

Author(s):

Hedieh Arshiany ◽

◽

Behzad Ezzatian ◽

Valentin Artounian ◽

Fatemeh Alizadeh ◽

...

Keyword(s):

Psychiatric Symptoms ◽

Late Onset ◽

Novel Mutation ◽

Disease Onset ◽

Disease Diagnosis ◽

Alexander Disease ◽

White Matter Hyperintensity ◽

Important Challenge ◽

Gene Study ◽

Exon Deletion

Introduction: Alexander disease is a heterogenous group of diseases with various manifestations based on age of disease onset. This rare leukodystrophy syndrome with mutations in GFAP Gene could present with developmental delay and seizure in infantile form to ataxia and bulbar palsy in adulthood. However psychiatric symptoms are not well-defined and usually evaluate after disease diagnosis not before disease investigations. Case report: Our patient is a fifty-two-year-old Iranian woman with history of depression from about 17 years ago, suicidal attempt two years ago and ingestion a large amount of opium with the intention of suicide 2 months ago who was presented with disorientation and probably delirious state in the last interview. Eventually in comprehensive investigations, white matter hyperintensity and leukodystrophy was diagnosed and ultimately to determine the cause of these changes with gene study, whole and Exon deletion of GFAP Gene Late Onset Alexander disease was determined. Conclusion: Neurological-onset manifestation of Alexander disease specifically late onset form is the most common clinical picture of disease and was seen in about 90% of patients but psychiatric symptoms are not well-known and psychiatric- onset disease was not described yet. On the other hand, various Gene Mutation were described in Late Onset Alexander Disease, however large whole Exon deletion which was revealed in our patient is a novel mutation and significantly need to be declared. Here authors describe a late onset Alexander disease with psychiatric onset symptoms and novel large Exon deletion in GFAP Gene.

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Abstract #492 Improvement in Muscle Strength and Psychiatric Symptoms in a Patient with Persistent Cushing Disease Treated with Mifepristone

Endocrine Practice ◽

10.1016/s1530-891x(20)46836-3 ◽

2019 ◽

Vol 25 ◽

pp. 242-243

Author(s):

Tamer Yacoub ◽

Kiruthi Palaniswamy

Keyword(s):

Muscle Strength ◽

Psychiatric Symptoms ◽

Cushing Disease

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Crisis Occurrence and Resolution in Patients with Severe and Persistent Mental Illness

Crisis ◽

10.1027/0227-5910.26.4.160 ◽

2005 ◽

Vol 26 (4) ◽

pp. 160-169 ◽

Cited By ~ 4

Author(s):

Paul S. Links ◽

Rahel Eynan ◽

Jeffrey S. Ball ◽

Aiala Barr ◽

Sean Rourke

Keyword(s):

Mental Illness ◽

Suicide Ideation ◽

Rating Scale ◽

Psychiatric Symptoms ◽

Self Report ◽

Community Treatment ◽

Persistent Mental Illness ◽

Crisis Events ◽

Symptom Distress Scale ◽

Distress Scale

Abstract. Assertive community treatment appears to have limited impact on the risk of suicide in persons with severe and persistent mental illness (SPMI). This exploratory prospective study attempts to understand this observation by studying the contribution of suicidality to the occurrence of crisis events in patients with SPMI. Specifically, an observer-rated measure of the need for hospitalization, the Crisis Triage Rating Scale, was completed at baseline, crisis occurrence, and resolution to determine how much the level of suicidality contributed to the deemed level of crisis. Second, observer-ratings of suicidal ideation, the Modified Scale for Suicide Ideation, and psychopathology and suicidality, Brief Psychiatric Rating Scale, were measured at baseline, crisis occurrence, and resolution. A self-report measure of distress, the Symptom Distress Scale, was completed at baseline, crisis occurrence, and resolution. Finally, the patients' crisis experiences were recorded qualitatively to compare with quantitative measures of suicidality. Almost 40% of the subjects experienced crisis events and more than a quarter of these events were judged to be severe enough to warrant the need for hospitalization. Our findings suggest that elevation of psychiatric symptoms is a major contributor to the crisis occurrences of individuals with SPMI; although the risk of suicide may have to be conceived as somewhat separate from crisis occurrence.

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Early Identification of Youth at Risk for Suicidal Behavior

Crisis ◽

10.1027/0227-5910/a000569 ◽

2019 ◽

Vol 40 (5) ◽

pp. 326-332

Author(s):

Ivonne Andrea Florez ◽

Devon LoParo ◽

Nakia Valentine ◽

Dorian A. Lamis

Keyword(s):

At Risk ◽

Early Identification ◽

Suicide Risk ◽

Psychiatric Symptoms ◽

Demographic Factors ◽

Health Centers ◽

Lack Of Information ◽

Youth At Risk ◽

Logistic Regressions ◽

Lethal Means

Abstract. Background: Early identification and appropriate referral services are priorities to prevent suicide. Aims: The aim of this study was to describe patterns of identification and referrals among three behavioral health centers and determine whether youth demographic factors and type of training received by providers were associated with identification and referral patterns. Method: The Early Identification Referral Forms were used to gather the data of interest among 820 youth aged 10–24 years who were screened for suicide risk (females = 53.8%). Descriptive statistics and binary logistic regressions were conducted to examine significant associations. Results: Significant associations between gender, race, and age and screening positive for suicide were found. Age and race were significantly associated with different patterns of referrals and/or services received by youths. For providers, being trained in Counseling on Access to Lethal Means was positively associated with number of referrals to inpatient services. Limitations: The correlational nature of the study and lack of information about suicide risk and comorbidity of psychiatric symptoms limit the implications of the findings. Conclusion: The results highlight the importance of considering demographic factors when identifying and referring youth at risk to ensure standard yet culturally appropriate procedures to prevent suicide.

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