Repetitive Suicidal Behaviors in a Case With a New Mutation of Wolfram Syndrome; A Jump From the Gene to The Behavior

Wolfram syndrome (WS) is a rare autosomal recessive neurodegenerative disease with variable symptoms including neuropsychiatric manifestations. A 26-year-old man was reported with classic symptoms of WS and repetitive psychiatric hospitalizations and at least 16 suicidal attempts. The genetic study demonstrated a novel homozygous stop-codon mutation on the WFS1 gene. This special type of mutation may be related to repetitive suicidal behaviors in this case of WS. Psychological support should be a routine practice in patients with WS.

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A novel nonsense mutation in the WFS1 gene causes the Wolfram syndrome

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2015-0045 ◽

2016 ◽

Vol 29 (5) ◽

Cited By ~ 1

Author(s):

Shahab Noorian ◽

Shahram Savad ◽

Davood Shah Mohammadi

Keyword(s):

Nonsense Mutation ◽

Autosomal Recessive ◽

Neurodegenerative Disorder ◽

Wolfram Syndrome ◽

Wfs1 Gene

AbstractWolfram syndrome is a rare autosomal recessive neurodegenerative disorder, which is mostly caused by mutations in the

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Funktionelle Relevanz der Stop-Codon Mutation rs61757459 in Vaspin (SerpinA12)

Diabetologie und Stoffwechsel ◽

10.1055/s-0033-1341836 ◽

2013 ◽

Vol 8 (S 01) ◽

Author(s):

J Breitfeld ◽

JT Heiker ◽

Y Böttcher ◽

D Schleinitz ◽

A Tönjes ◽

...

Keyword(s):

Stop Codon ◽

Stop Codon Mutation ◽

Codon Mutation

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A Case of Congenital Glucose Galactose Malabsorption with a New Mutation in the SLC5A1 Gene

Journal of Pediatric Genetics ◽

10.1055/s-0040-1719161 ◽

2020 ◽

Author(s):

Hasan Akduman ◽

Dilek Dilli ◽

Serdar Ceylaner

Keyword(s):

Mutation Analysis ◽

Autosomal Recessive ◽

Glucose Transporter ◽

Neonatal Period ◽

Autosomal Recessive Disorder ◽

Homozygous Mutation ◽

New Mutation ◽

Early Neonatal Period ◽

Sodium Dependent ◽

Hypernatremic Dehydration

AbstractCongenital glucose-galactose malabsorption (CGGM) is an autosomal recessive disorder originating from an abnormal transporter mechanism in the intestines. It was sourced from a mutation in the SLC5A1 gene, which encodes a sodium-dependent glucose transporter. Here we report a 2-day-old girl with CGGM who presented with severe hypernatremic dehydration due to diarrhea beginning in the first hours of life. Mutation analysis revealed a novel homozygous mutation NM_000343.3 c.127G > A (p.Gly43Arg) in the SLC5A1 gene. Since CGGM can cause fatal diarrhea in the early neonatal period, timely diagnosis of the disease seems to be essential.

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Novel mutations in the WFS1 gene are associated with Wolfram syndrome and systemic inflammation

Human Molecular Genetics ◽

10.1093/hmg/ddab040 ◽

2021 ◽

Author(s):

Eleonora Panfili ◽

Giada Mondanelli ◽

Ciriana Orabona ◽

Maria L Belladonna ◽

Marco Gargaro ◽

...

Keyword(s):

Er Stress ◽

Mononuclear Cells ◽

Autosomal Recessive Disorder ◽

Wolfram Syndrome ◽

Therapeutic Interventions ◽

T Helper 17 ◽

Gene Encoding ◽

Peripheral Blood Mononuclear ◽

Inflammatory State ◽

Wfs1 Gene

Abstract Mutations in the WFS1 gene, encoding wolframin (WFS1), cause endoplasmic reticulum (ER) stress and are associated with a rare autosomal-recessive disorder known as Wolfram syndrome (WS). WS is clinically characterized by childhood-onset diabetes mellitus, optic atrophy, deafness, diabetes insipidus and neurological signs. We identified two novel WFS1 mutations in a patient with WS, namely, c.316-1G > A (in intron 3) and c.757A > T (in exon 7). Both mutations, located in the N-terminal region of the protein, were predicted to generate a truncated and inactive form of WFS1. We found that although the WFS1 protein was not expressed in peripheral blood mononuclear cells (PBMCs) of the proband, no constitutive ER stress activation could be detected in those cells. In contrast, WS proband’s PBMCs produced very high levels of proinflammatory cytokines (i.e. TNF-α, IL-1β, and IL-6) in the absence of any stimulus. WFS1 silencing in PBMCs from control subjects by means of small RNA interference also induced a pronounced proinflammatory cytokine profile. The same cytokines were also significantly higher in sera from the WS patient as compared to matched healthy controls. Moreover, the chronic inflammatory state was associated with a dominance of proinflammatory T helper 17 (Th17)-type cells over regulatory T (Treg) lymphocytes in the WS PBMCs. The identification of a state of systemic chronic inflammation associated with WFS1 deficiency may pave the way to innovative and personalized therapeutic interventions in WS.

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