scholarly journals De novo and inherited mutations in the X-linked gene CLCN4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females

2016 ◽  
Vol 23 (2) ◽  
pp. 222-230 ◽  
Author(s):  
E E Palmer ◽  
◽  
T Stuhlmann ◽  
S Weinert ◽  
E Haan ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Linked Gene ◽  
Seizure Disorders ◽  
Males And Females ◽  
And Behavior ◽  
Inherited Mutations

A de novo 10p11.23-p12.1 deletion recapitulates the phenotype observed inWACmutations and strengthens the role ofWACin intellectual disability and behavior disorders

2016 ◽  
Vol 170 (7) ◽  
pp. 1912-1917 ◽  
Author(s):  
Fatma Abdelhedi ◽  
Laila El Khattabi ◽  
Nouha Essid ◽  
Geraldine Viot ◽  
Dominique Letessier ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Behavior Disorders ◽  
De Novo ◽  
And Behavior

scholarly journals A novel de novo DDX3X missense variant in a female with brachycephaly and intellectual disability: a case report

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Giada Moresco ◽  
Jole Costanza ◽  
Carlo Santaniello ◽  
Ornella Rondinone ◽  
Federico Grilli ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Clinical Presentation ◽  
De Novo ◽  
Clinical Signs ◽  
Missense Variant ◽  
Psychomotor Development ◽  
Helicase Domain ◽  
Protein Activity ◽  
Mrna Metabolism ◽  
Pathogenic Variants

Abstract Background De novo pathogenic variants in the DDX3X gene are reported to account for 1–3% of unexplained intellectual disability (ID) in females, leading to the rare disease known as DDX3X syndrome (MRXSSB, OMIM #300958). Besides ID, these patients manifest a variable clinical presentation, which includes neurological and behavioral defects, and abnormal brain MRIs. Case presentation We report a 10-year-old girl affected by delayed psychomotor development, delayed myelination, and polymicrogyria (PMG). We identified a novel de novo missense mutation in the DDX3X gene (c.625C > G) by whole exome sequencing (WES). The DDX3X gene encodes a DEAD-box ATP-dependent RNA-helicase broadly implicated in gene expression through regulation of mRNA metabolism. The identified mutation is located just upstream the helicase domain and is suggested to impair the protein activity, thus resulting in the altered translation of DDX3X-dependent mRNAs. The proband, presenting with the typical PMG phenotype related to the syndrome, does not show other clinical signs frequently reported in presence of missense DDX3X mutations that are associated with a most severe clinical presentation. In addition, she has brachycephaly, never described in female DDX3X patients, and macroglossia, that has never been associated with the syndrome. Conclusions This case expands the knowledge of DDX3X pathogenic variants and the associated DDX3X syndrome phenotypic spectrum.

scholarly journals Neuronal Cytoskeleton in Intellectual Disability: From Systems Biology and Modeling to Therapeutic Opportunities

2021 ◽  
Vol 22 (11) ◽  
pp. 6167
Author(s):  
Carla Liaci ◽  
Mattia Camera ◽  
Giovanni Caslini ◽  
Simona Rando ◽  
Salvatore Contino ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Systems Biology ◽  
Rho Gtpases ◽  
Current Knowledge ◽  
Pathological Condition ◽  
Hierarchical Arrangement ◽  
Worldwide Population ◽  
Id Genes ◽  
Effective Network ◽  
And Behavior

Intellectual disability (ID) is a pathological condition characterized by limited intellectual functioning and adaptive behaviors. It affects 1–3% of the worldwide population, and no pharmacological therapies are currently available. More than 1000 genes have been found mutated in ID patients pointing out that, despite the common phenotype, the genetic bases are highly heterogeneous and apparently unrelated. Bibliomic analysis reveals that ID genes converge onto a few biological modules, including cytoskeleton dynamics, whose regulation depends on Rho GTPases transduction. Genetic variants exert their effects at different levels in a hierarchical arrangement, starting from the molecular level and moving toward higher levels of organization, i.e., cell compartment and functions, circuits, cognition, and behavior. Thus, cytoskeleton alterations that have an impact on cell processes such as neuronal migration, neuritogenesis, and synaptic plasticity rebound on the overall establishment of an effective network and consequently on the cognitive phenotype. Systems biology (SB) approaches are more focused on the overall interconnected network rather than on individual genes, thus encouraging the design of therapies that aim to correct common dysregulated biological processes. This review summarizes current knowledge about cytoskeleton control in neurons and its relevance for the ID pathogenesis, exploiting in silico modeling and translating the implications of those findings into biomedical research.

scholarly journals Evolutionary Patterns of Sex-Biased Genes in Three Species of Haplodiploid Insects

Insects ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 326
Author(s):  
Yu-Jun Wang ◽  
Hua-Ling Wang ◽  
Xiao-Wei Wang ◽  
Shu-Sheng Liu
Keyword(s):  
Gene Expression ◽  
Slow Rate ◽  
Species Complex ◽  
Evolutionary Patterns ◽  
Protein Coding ◽  
Coding Sequences ◽  
Species Comparisons ◽  
Differential Gene ◽  
Males And Females ◽  
And Behavior

Females and males often differ obviously in morphology and behavior, and the differences between sexes are the result of natural selection and/or sexual selection. To a great extent, the differences between the two sexes are the result of differential gene expression. In haplodiploid insects, this phenomenon is obvious, since males develop from unfertilized zygotes and females develop from fertilized zygotes. Whiteflies of the Bemisia tabaci species complex are typical haplodiploid insects, and some species of this complex are important pests of many crops worldwide. Here, we report the transcriptome profiles of males and females in three species of this whitefly complex. Between-species comparisons revealed that non-sex-biased genes display higher variation than male-biased or female-biased genes. Sex-biased genes evolve at a slow rate in protein coding sequences and gene expression and have a pattern of evolution that differs from those of social haplodiploid insects and diploid animals. Genes with high evolutionary rates are more related to non-sex-biased traits—such as nutrition, immune system, and detoxification—than to sex-biased traits, indicating that the evolution of protein coding sequences and gene expression has been mainly driven by non-sex-biased traits.

Identification of a patient with intellectual disability and de novo 3.7Mb deletion supports the existence of a novel microdeletion syndrome in 2p14–p15

Gene ◽  
2013 ◽  
Vol 516 (1) ◽  
pp. 158-161 ◽  
Author(s):  
Miroslava Hancarova ◽  
Sarka Vejvalkova ◽  
Marie Trkova ◽  
Jana Drabova ◽  
Alzbeta Dleskova ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Microdeletion Syndrome

scholarly journals De Novo Mutations in the Genome Organizer CTCF Cause Intellectual Disability

2013 ◽  
Vol 93 (1) ◽  
pp. 124-131 ◽  
Author(s):  
Anne Gregor ◽  
Martin Oti ◽  
Evelyn N. Kouwenhoven ◽  
Juliane Hoyer ◽  
Heinrich Sticht ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
De Novo Mutations

scholarly journals Müllerian inhibiting substance contributes to sex-linked biases in the brain and behavior

2009 ◽  
Vol 106 (17) ◽  
pp. 7203-7208 ◽  
Author(s):  
Pei-Yu Wang ◽  
Anna Protheroe ◽  
Andrew N. Clarkson ◽  
Floriane Imhoff ◽  
Kyoko Koishi ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Reproductive Tract ◽  
Behavioral Traits ◽  
Spinal Motor Neurons ◽  
Müllerian Inhibiting Substance ◽  
Males And Females ◽  
Brain And Behavior ◽  
And Behavior ◽  
The Brain ◽  
Mullerian Inhibiting Substance

Many behavioral traits and most brain disorders are common to males and females but are more evident in one sex than the other. The control of these subtle sex-linked biases is largely unstudied and has been presumed to mirror that of the highly dimorphic reproductive nuclei. Sexual dimorphism in the reproductive tract is a product of Müllerian inhibiting substance (MIS), as well as the sex steroids. Males with a genetic deficiency in MIS signaling are sexually males, leading to the presumption that MIS is not a neural regulator. We challenge this presumption by reporting that most immature neurons in mice express the MIS-specific receptor (MISRII) and that male Mis−/− and Misrii−/− mice exhibit subtle feminization of their spinal motor neurons and of their exploratory behavior. Consequently, MIS may be a broad regulator of the subtle sex-linked biases in the nervous system.

IL1RAPL1 Gene Deletion in a Female Patient with Developmental Delay and Continuous Spike-Wave during Sleep

2021 ◽  
Author(s):  
Evan Jiang ◽  
Mark P. Fitzgerald ◽  
Katherine L. Helbig ◽  
Ethan M. Goldberg
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Synapse Formation ◽  
De Novo ◽  
Interleukin 1 ◽  
Autism Spectrum ◽  
Neurological Dysfunction ◽  
Behavioral Disorder ◽  
Clinical Genetic ◽  
Severe Intellectual Disability

AbstractInterleukin-1 receptor accessory protein-like 1 (IL1RAPL1) encodes a protein that is highly expressed in neurons and has been shown to regulate neurite outgrowth as well as synapse formation and synaptic transmission. Clinically, mutations in or deletions of IL1RAPL1 have been associated with a spectrum of neurological dysfunction including autism spectrum disorder and nonsyndromic X-linked developmental delay/intellectual disability of varying severity. Nearly all reported cases are in males; in the few reported cases involving females, the clinical presentation was mild or the deletion was identified in phenotypically normal carriers in accordance with X-linked inheritance. Using genome-wide microarray analysis, we identified a novel de novo 373 kb interstitial deletion of the X chromosome (Xp21.1-p21.2) that includes exons 4 to 6 of the IL1RAPL1 gene in an 8-year-old girl with severe intellectual disability and behavioral disorder with a history of developmental regression. Overnight continuous video electroencephalography revealed electrical status epilepticus in sleep (ESES). This case expands the clinical genetic spectrum of IL1RAPL1-related neurodevelopmental disorders and highlights a new genetic association of ESES.

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