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Mechanisms and Interventions for Neurological and Psychological Disorders 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 34484

Special Issue Editors


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Institute for Health and Sport, Victoria University, Melbourne, VIC 3021, Australia
Interests: nanoparticles; vaccines; depression; neuroimmunology; gut-brain axis; neuropsychiatric disorders
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Guest Editor
Institute for Health and Sport, Victoria University, Melbourne, VIC 3011, Australia
Interests: immunology; protein crystallography; medicinal chemistry; cellular and molecular biology; extensive translational research; clinical trials; vaccines; drugs; healthy ageing; chronic diseases; inflammation
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
AIMSS, Department of Neurology, Melbourne Medical School, Sunshine Hospital, Western Health, The University of Melbourne, Melbourne, VIC 3011, Australia
Interests: migraine; brain injury; stroke; neurology; headache
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neurological conditions affect the brain, the spinal cord, and nerves found throughout the body. There are over 600 neurological conditions that affect humans, including dementia, epilepsy, multiple sclerosis, motor neuron disease, and headache (see keywords for other neurological disorder examples). Abnormalities in the brain, spinal cord, or nerves, including structural, biochemical, or electrical, lead to symptoms of a neurological condition. Some symptoms include muscle weakness, loss of coordination and sensation, seizures, paralysis, etc. The causes of neurological disorders vary but can be due to infections, tumors, environmental, lifestyle, genetic, congenital, and trauma.

There is also a vast range of psychological disorders, which include bipolar, eating disorders, paranoia, psychosis, schizophrenia, social anxiety disorder, phobias, agoraphobia, panic attacks, and neuropsychiatric disorders. These disorders can be genetic, biological, viral, and chemical, or be a result of chemical imbalances in the brain, traumatic brain injury, a history of abuse, stress, cancer, alcohol, or recreational substance abuse.

This Special Issue aims to collect contributions related to mechanisms of disease including at the molecular, cellular, genetic, biochemical, and immunological levels. We also seek articles on interventions used to manage these disorders.

You are invited to submit original experimental research papers, theoretical papers, reviews, systematic reviews, meta-analyses, communications, reports, and notes. We look forward to receiving your contributions.

Dr. Majid Davidson
Prof. Dr. Vasso Apostolopoulos
Prof. Dr. Tissa Wijeratne
Guest Editors

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Keywords

  • cerebral palsy

  • headaches
  • stroke
  • Bell’s palsy
  • neurodegeneration
  • dementia
  • Parkinson’s disease
  • Alzheimer’s disease
  • Huntington’s disease
  • Guillain–Barre syndrome
  • multiple sclerosis
  • brain cancer
  • myasthenia gravis
  • neuromuscular disorders
  • muscular dystrophy
  • amyotrophic lateral sclerosis
  • motor neuron disease
  • neurodevelopment disorders
  • learning disabilities
  • autism
  • mental retardation
  • attention deficit disorder
  • ataxia
  • epilepsy, seizures
  • gut-brain axis
  • traumatic brain injury
  • Tourette syndrome
  • shingles
  • meningitis
  • encephalitis
  • psychological disorder
  • bipolar
  • eating disorders
  • paranoia
  • psychosis
  • schizophrenia
  • neuropsychiatric disorder
  • depression, anxiety
  • ageing
  • virus infections
  • cancer
  • molecular
  • cellular
  • immunological aspects
  • genetic
  • interventions
  • mechanisms

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Related Special Issue

Published Papers (11 papers)

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Research

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23 pages, 4176 KiB  
Article
Beyond Motor Deficits: Environmental Enrichment Mitigates Huntington’s Disease Effects in YAC128 Mice
by Evelini Plácido, Priscilla Gomes Welter, Ana Wink, Gabriela Duarte Karasiak, Tiago Fleming Outeiro, Alcir Luiz Dafre, Joana Gil-Mohapel and Patricia S. Brocardo
Int. J. Mol. Sci. 2023, 24(16), 12607; https://doi.org/10.3390/ijms241612607 - 9 Aug 2023
Cited by 2 | Viewed by 1582
Abstract
Huntington’s disease (HD) is a neurodegenerative genetic disorder characterized by motor, psychiatric, cognitive, and peripheral symptoms without effective therapy. Evidence suggests that lifestyle factors can modulate disease onset and progression, and environmental enrichment (EE) has emerged as a potential approach to mitigate the [...] Read more.
Huntington’s disease (HD) is a neurodegenerative genetic disorder characterized by motor, psychiatric, cognitive, and peripheral symptoms without effective therapy. Evidence suggests that lifestyle factors can modulate disease onset and progression, and environmental enrichment (EE) has emerged as a potential approach to mitigate the progression and severity of neurodegenerative processes. Wild-type (WT) and yeast artificial chromosome (YAC) 128 mice were exposed to different EE conditions. Animals from cohort 1 were exposed to EE between postnatal days 21 and 60, and animals from cohort 2 were exposed to EE between postnatal days 60 and 120. Motor and non-motor behavioral tests were employed to evaluate the effects of EE on HD progression. Monoamine levels, hippocampal cell proliferation, neuronal differentiation, and dendritic arborization were also assessed. Here we show that EE had an antidepressant-like effect and slowed the progression of motor deficits in HD mice. It also reduced monoamine levels, which correlated with better motor performance, particularly in the striatum. EE also modulated neuronal differentiation in the YAC128 hippocampus. These results confirm that EE can impact behavior, hippocampal neuroplasticity, and monoamine levels in YAC128 mice, suggesting this could be a therapeutic strategy to modulate neuroplasticity deficits in HD. However, further research is needed to fully understand EE’s mechanisms and long-term effects as an adjuvant therapy for this debilitating condition. Full article
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13 pages, 6246 KiB  
Article
Otilonium Bromide Prevents Cholinergic Changes in the Distal Colon Induced by Chronic Water Avoidance Stress, a Rat Model of Irritable Bowel Syndrome
by Chiara Traini, Eglantina Idrizaj, Cristina Biagioni, Maria Caterina Baccari and Maria Giuliana Vannucchi
Int. J. Mol. Sci. 2023, 24(8), 7440; https://doi.org/10.3390/ijms24087440 - 18 Apr 2023
Cited by 2 | Viewed by 1945
Abstract
Irritable Bowel syndrome (IBS) is a highly widespread gastrointestinal disorder whose symptomatology mainly affect the large intestine. Among the risk factors, psychosocial stress is the most acknowledged. The repeated water avoidance stress (rWAS) is considered an animal model of psychosocial stress that is [...] Read more.
Irritable Bowel syndrome (IBS) is a highly widespread gastrointestinal disorder whose symptomatology mainly affect the large intestine. Among the risk factors, psychosocial stress is the most acknowledged. The repeated water avoidance stress (rWAS) is considered an animal model of psychosocial stress that is capable of mimicking IBS. Otilonium bromide (OB), which is orally administered, concentrates in the large bowel and controls most of the IBS symptoms in humans. Several reports have shown that OB has multiple mechanisms of action and cellular targets. We investigated whether the application of rWAS to rats induced morphological and functional alterations of the cholinergic neurotransmission in the distal colon and whether OB prevented them. The results demonstrated that rWAS affects cholinergic neurotransmission by causing an increase in acid mucin secretion, in the amplitude of electrically evoked contractile responses, abolished by atropine, and in the number of myenteric neurons expressing choline acetyltransferase. OB counteracted these changes and also showed an intrinsic antimuscarinic effect on the post-synaptic muscular receptors. We assume that the rWAS consequences on the cholinergic system are linked to corticotrophin-releasing factor-1 (CRF1) receptor activation by the CRF hypothalamic hormone. OB, by interfering with the CFR/CRFr activation, interrupted the cascade events responsible for the changes affecting the rWAS rat colon. Full article
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18 pages, 3964 KiB  
Article
Profiling and Cellular Analyses of Obesity-Related circRNAs in Neurons and Glia under Obesity-like In Vitro Conditions
by Danbi Jo, Gwangho Yoon, Yeonghwan Lim, Youngkook Kim and Juhyun Song
Int. J. Mol. Sci. 2023, 24(7), 6235; https://doi.org/10.3390/ijms24076235 - 25 Mar 2023
Viewed by 2419
Abstract
Recent evidence indicates that the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease, is associated with metabolic disorders such as diabetes and obesity. Various circular RNAs (circRNAs) have been found in brain tissues and recent studies have suggested that circRNAs are related to neuropathological [...] Read more.
Recent evidence indicates that the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease, is associated with metabolic disorders such as diabetes and obesity. Various circular RNAs (circRNAs) have been found in brain tissues and recent studies have suggested that circRNAs are related to neuropathological mechanisms in the brain. However, there is a lack of interest in the involvement of circRNAs in metabolic imbalance-related neuropathological problems until now. Herein we profiled and analyzed diverse circRNAs in mouse brain cell lines (Neuro-2A neurons, BV-2 microglia, and C8-D1a astrocytes) exposed to obesity-related in vitro conditions (high glucose, high insulin, and high levels of tumor necrosis factor-alpha, interleukin 6, palmitic acid, linoleic acid, and cholesterol). We observed that various circRNAs were differentially expressed according to cell types with many of these circRNAs conserved in humans. After suppressing the expression of these circRNAs using siRNAs, we observed that these circRNAs regulate genes related to inflammatory responses, formation of synaptic vesicles, synaptic density, and fatty acid oxidation in neurons; scavenger receptors in microglia; and fatty acid signaling, inflammatory signaling cyto that may play important roles in metabolic disorders associated with neurodegenerative diseases. Full article
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Review

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32 pages, 6181 KiB  
Review
Adult Neurogenesis of Teleost Fish Determines High Neuronal Plasticity and Regeneration
by Evgeniya Vladislavovna Pushchina, Ilya Alexandovich Kapustyanov and Gleb Gennadievich Kluka
Int. J. Mol. Sci. 2024, 25(7), 3658; https://doi.org/10.3390/ijms25073658 - 25 Mar 2024
Cited by 1 | Viewed by 1446
Abstract
Studying the properties of neural stem progenitor cells (NSPCs) in a fish model will provide new information about the organization of neurogenic niches containing embryonic and adult neural stem cells, reflecting their development, origin cell lines and proliferative dynamics. Currently, the molecular signatures [...] Read more.
Studying the properties of neural stem progenitor cells (NSPCs) in a fish model will provide new information about the organization of neurogenic niches containing embryonic and adult neural stem cells, reflecting their development, origin cell lines and proliferative dynamics. Currently, the molecular signatures of these populations in homeostasis and repair in the vertebrate forebrain are being intensively studied. Outside the telencephalon, the regenerative plasticity of NSPCs and their biological significance have not yet been practically studied. The impressive capacity of juvenile salmon to regenerate brain suggests that most NSPCs are likely multipotent, as they are capable of replacing virtually all cell lineages lost during injury, including neuroepithelial cells, radial glia, oligodendrocytes, and neurons. However, the unique regenerative profile of individual cell phenotypes in the diverse niches of brain stem cells remains unclear. Various types of neuronal precursors, as previously shown, are contained in sufficient numbers in different parts of the brain in juvenile Pacific salmon. This review article aims to provide an update on NSPCs in the brain of common models of zebrafish and other fish species, including Pacific salmon, and the involvement of these cells in homeostatic brain growth as well as reparative processes during the postraumatic period. Additionally, new data are presented on the participation of astrocytic glia in the functioning of neural circuits and animal behavior. Thus, from a molecular aspect, zebrafish radial glia cells are seen to be similar to mammalian astrocytes, and can therefore also be referred to as astroglia. However, a question exists as to if zebrafish astroglia cells interact functionally with neurons, in a similar way to their mammalian counterparts. Future studies of this fish will complement those on rodents and provide important information about the cellular and physiological processes underlying astroglial function that modulate neural activity and behavior in animals. Full article
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28 pages, 3605 KiB  
Review
Gold Nanoparticles in Neurological Diseases: A Review of Neuroprotection
by Ming-Chang Chiang, Yu-Ping Yang, Christopher J. B. Nicol and Chieh-Ju Wang
Int. J. Mol. Sci. 2024, 25(4), 2360; https://doi.org/10.3390/ijms25042360 - 17 Feb 2024
Cited by 6 | Viewed by 2940
Abstract
This review explores the diverse applications of gold nanoparticles (AuNPs) in neurological diseases, with a specific focus on Alzheimer’s disease (AD), Parkinson’s disease (PD), and stroke. The introduction highlights the pivotal role of neuroinflammation in these disorders and introduces the unique properties of [...] Read more.
This review explores the diverse applications of gold nanoparticles (AuNPs) in neurological diseases, with a specific focus on Alzheimer’s disease (AD), Parkinson’s disease (PD), and stroke. The introduction highlights the pivotal role of neuroinflammation in these disorders and introduces the unique properties of AuNPs. The review’s core examines the mechanisms by which AuNPs exert neuroprotection and anti-neuro-inflammatory effects, elucidating various pathways through which they manifest these properties. The potential therapeutic applications of AuNPs in AD are discussed, shedding light on promising avenues for therapy. This review also explores the prospects of utilizing AuNPs in PD interventions, presenting a hopeful outlook for future treatments. Additionally, the review delves into the potential of AuNPs in providing neuroprotection after strokes, emphasizing their significance in mitigating cerebrovascular accidents’ aftermath. Experimental findings from cellular and animal models are consolidated to provide a comprehensive overview of AuNPs’ effectiveness, offering insights into their impact at both the cellular and in vivo levels. This review enhances our understanding of AuNPs’ applications in neurological diseases and lays the groundwork for innovative therapeutic strategies in neurology. Full article
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19 pages, 1618 KiB  
Review
Insights into the Role of Histone Methylation in Brain Aging and Potential Therapeutic Interventions
by Nikolaos Vitorakis and Christina Piperi
Int. J. Mol. Sci. 2023, 24(24), 17339; https://doi.org/10.3390/ijms242417339 - 11 Dec 2023
Cited by 4 | Viewed by 2183
Abstract
Epigenetic mechanisms play a primary role in the cellular damage associated with brain aging. Histone posttranslational modifications represent intrinsic molecular alterations essential for proper physiological functioning, while divergent expression and activity have been detected in several aspects of brain aging. Aberrant histone methylation [...] Read more.
Epigenetic mechanisms play a primary role in the cellular damage associated with brain aging. Histone posttranslational modifications represent intrinsic molecular alterations essential for proper physiological functioning, while divergent expression and activity have been detected in several aspects of brain aging. Aberrant histone methylation has been involved in neural stem cell (NSC) quiescence, microglial deficits, inflammatory processes, memory impairment, cognitive decline, neurodegenerative diseases, and schizophrenia. Herein, we provide an overview of recent studies on epigenetic regulation of brain tissue aging, mainly focusing on the role of histone methylation in different cellular and functional aspects of the aging process. Emerging targeting strategies of histone methylation are further explored, including neuroprotective drugs, natural compounds, and lifestyle modifications with therapeutic potential towards the aging process of the brain. Full article
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27 pages, 1377 KiB  
Review
The Role of Adipokines in the Pathologies of the Central Nervous System
by Korbinian Huber, Emilia Szerenos, Dawid Lewandowski, Kacper Toczylowski and Artur Sulik
Int. J. Mol. Sci. 2023, 24(19), 14684; https://doi.org/10.3390/ijms241914684 - 28 Sep 2023
Cited by 5 | Viewed by 1655
Abstract
Adipokines are protein hormones secreted by adipose tissue in response to disruptions in physiological homeostasis within the body’s systems. The regulatory functions of adipokines within the central nervous system (CNS) are multifaceted and intricate, and they have been identified in a number of [...] Read more.
Adipokines are protein hormones secreted by adipose tissue in response to disruptions in physiological homeostasis within the body’s systems. The regulatory functions of adipokines within the central nervous system (CNS) are multifaceted and intricate, and they have been identified in a number of pathologies. Therefore, specific adipokines have the potential to be used as biomarkers for screening purposes in neurological dysfunctions. The systematic review presented herein focuses on the analysis of the functions of various adipokines in the pathogenesis of CNS diseases. Thirteen proteins were selected for analysis through scientific databases. It was found that these proteins can be identified within the cerebrospinal fluid either by their ability to modify their molecular complex and cross the blood–brain barrier or by being endogenously produced within the CNS itself. As a result, this can correlate with their measurability during pathological processes, including Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis, depression, or brain tumors. Full article
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31 pages, 1551 KiB  
Review
Zebrafish as an Innovative Tool for Epilepsy Modeling: State of the Art and Potential Future Directions
by Marta D’Amora, Alessandro Galgani, Maria Marchese, Francesco Tantussi, Ugo Faraguna, Francesco De Angelis and Filippo Sean Giorgi
Int. J. Mol. Sci. 2023, 24(9), 7702; https://doi.org/10.3390/ijms24097702 - 22 Apr 2023
Cited by 6 | Viewed by 3269
Abstract
This article discusses the potential of Zebrafish (ZF) (Danio Rerio), as a model for epilepsy research. Epilepsy is a neurological disorder affecting both children and adults, and many aspects of this disease are still poorly understood. In vivo and in vitro models derived [...] Read more.
This article discusses the potential of Zebrafish (ZF) (Danio Rerio), as a model for epilepsy research. Epilepsy is a neurological disorder affecting both children and adults, and many aspects of this disease are still poorly understood. In vivo and in vitro models derived from rodents are the most widely used for studying both epilepsy pathophysiology and novel drug treatments. However, researchers have recently obtained several valuable insights into these two fields of investigation by studying ZF. Despite the relatively simple brain structure of these animals, researchers can collect large amounts of data in a much shorter period and at lower costs compared to classical rodent models. This is particularly useful when a large number of candidate antiseizure drugs need to be screened, and ethical issues are minimized. In ZF, seizures have been induced through a variety of chemoconvulsants, primarily pentylenetetrazol (PTZ), kainic acid (KA), and pilocarpine. Furthermore, ZF can be easily genetically modified to test specific aspects of monogenic forms of human epilepsy, as well as to discover potential convulsive phenotypes in monogenic mutants. The article reports on the state-of-the-art and potential new fields of application of ZF research, including its potential role in revealing epileptogenic mechanisms, rather than merely assessing iatrogenic acute seizure modulation. Full article
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24 pages, 1481 KiB  
Review
Impact of Pesticide Residues on the Gut-Microbiota–Blood–Brain Barrier Axis: A Narrative Review
by Maria Abou Diwan, Marwa Lahimer, Véronique Bach, Fabien Gosselet, Hafida Khorsi-Cauet and Pietra Candela
Int. J. Mol. Sci. 2023, 24(7), 6147; https://doi.org/10.3390/ijms24076147 - 24 Mar 2023
Cited by 11 | Viewed by 4977
Abstract
Accumulating evidence indicates that chronic exposure to a low level of pesticides found in diet affects the human gut-microbiota–blood–brain barrier (BBB) axis. This axis describes the physiological and bidirectional connection between the microbiota, the intestinal barrier (IB), and the BBB. Preclinical observations reported [...] Read more.
Accumulating evidence indicates that chronic exposure to a low level of pesticides found in diet affects the human gut-microbiota–blood–brain barrier (BBB) axis. This axis describes the physiological and bidirectional connection between the microbiota, the intestinal barrier (IB), and the BBB. Preclinical observations reported a gut microbial alteration induced by pesticides, also known as dysbiosis, a condition associated not only with gastrointestinal disorders but also with diseases affecting other distal organs, such as the BBB. However, the interplay between pesticides, microbiota, the IB, and the BBB is still not fully explored. In this review, we first consider the similarities/differences between these two physiological barriers and the different pathways that link the gut microbiota and the BBB to better understand the dialogue between bacteria and the brain. We then discuss the effects of chronic oral pesticide exposure on the gut-microbiota-BBB axis and raise awareness of the danger of chronic exposure, especially during the perinatal period (pregnant women and offspring). Full article
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17 pages, 2810 KiB  
Review
Tryptophan and Substance Abuse: Mechanisms and Impact
by Majid Davidson, Niloufar Rashidi, Md Kamal Hossain, Ali Raza, Kulmira Nurgali and Vasso Apostolopoulos
Int. J. Mol. Sci. 2023, 24(3), 2737; https://doi.org/10.3390/ijms24032737 - 1 Feb 2023
Cited by 5 | Viewed by 9362
Abstract
Addiction, the continuous misuse of addictive material, causes long-term dysfunction in the neurological system. It substantially affects the control strength of reward, memory, and motivation. Addictive substances (alcohol, marijuana, caffeine, heroin, methamphetamine (METH), and nicotine) are highly active central nervous stimulants. Addiction leads [...] Read more.
Addiction, the continuous misuse of addictive material, causes long-term dysfunction in the neurological system. It substantially affects the control strength of reward, memory, and motivation. Addictive substances (alcohol, marijuana, caffeine, heroin, methamphetamine (METH), and nicotine) are highly active central nervous stimulants. Addiction leads to severe health issues, including cardiovascular diseases, serious infections, and pulmonary/dental diseases. Drug dependence may result in unfavorable cognitive impairments that can continue during abstinence and negatively influence recovery performance. Although addiction is a critical global health challenge with numerous consequences and complications, currently, there are no efficient options for treating drug addiction, particularly METH. Currently, novel treatment approaches such as psychological contingency management, cognitive behavioral therapy, and motivational enhancement strategies are of great interest. Herein, we evaluate the devastating impacts of different addictive substances/drugs on users′ mental health and the role of tryptophan in alleviating unfavorable side effects. The tryptophan metabolites in the mammalian brain and their potential to treat compulsive abuse of addictive substances are investigated by assessing the functional effects of addictive substances on tryptophan. Future perspectives on developing promising modalities to treat addiction and the role of tryptophan and its metabolites to alleviate drug dependency are discussed. Full article
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Other

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10 pages, 844 KiB  
Brief Report
Biallelic Loss-of-Function Variants in BICD1 Are Associated with Peripheral Neuropathy and Hearing Loss
by Yoel Hirsch, Wendy K. Chung, Sergey Novoselov, Louis H. Weimer, Alexander Rossor, Charles A. LeDuc, Amanda J. McPartland, Ernesto Cabrera, Josef Ekstein, Sholem Scher, Rick F. Nelson, Giampietro Schiavo, Lindsay B. Henderson and Kevin T. A. Booth
Int. J. Mol. Sci. 2023, 24(10), 8897; https://doi.org/10.3390/ijms24108897 - 17 May 2023
Viewed by 1661
Abstract
Hearing loss and peripheral neuropathy are two clinical entities that are genetically and phenotypically heterogeneous and sometimes co-occurring. Using exome sequencing and targeted segregation analysis, we investigated the genetic etiology of peripheral neuropathy and hearing loss in a large Ashkenazi Jewish family. Moreover, [...] Read more.
Hearing loss and peripheral neuropathy are two clinical entities that are genetically and phenotypically heterogeneous and sometimes co-occurring. Using exome sequencing and targeted segregation analysis, we investigated the genetic etiology of peripheral neuropathy and hearing loss in a large Ashkenazi Jewish family. Moreover, we assessed the production of the candidate protein via western blotting of lysates from fibroblasts from an affected individual and an unaffected control. Pathogenic variants in known disease genes associated with hearing loss and peripheral neuropathy were excluded. A homozygous frameshift variant in the BICD1 gene, c.1683dup (p.(Arg562Thrfs*18)), was identified in the proband and segregated with hearing loss and peripheral neuropathy in the family. The BIDC1 RNA analysis from patient fibroblasts showed a modest reduction in gene transcripts compared to the controls. In contrast, protein could not be detected in fibroblasts from a homozygous c.1683dup individual, whereas BICD1 was detected in an unaffected individual. Our findings indicate that bi-allelic loss-of-function variants in BICD1 are associated with hearing loss and peripheral neuropathy. Definitive evidence that bi-allelic loss-of-function variants in BICD1 cause peripheral neuropathy and hearing loss will require the identification of other families and individuals with similar variants with the same phenotype. Full article
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