scholarly journals GeneMatcher Aids in the Identification of a New Malformation Syndrome with Intellectual Disability, Unique Facial Dysmorphisms, and Skeletal and Connective Tissue Abnormalities Caused by De Novo Variants inHNRNPK

2015 ◽  
Vol 36 (10) ◽  
pp. 1009-1014 ◽  
Author(s):  
P. Y. Billie Au ◽  
Jing You ◽  
Oana Caluseriu ◽  
Jeremy Schwartzentruber ◽  
Jacek Majewski ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Connective Tissue ◽  
De Novo ◽  
Malformation Syndrome ◽  
Facial Dysmorphisms ◽  
Tissue Abnormalities

Haploinsufficiency of XPO1 and USP34 by a de novo 230 kb deletion in 2p15, in a patient with mild intellectual disability and cranio-facial dysmorphisms

2014 ◽  
Vol 57 (9) ◽  
pp. 513-519 ◽  
Author(s):  
Madeleine Fannemel ◽  
Tuva Barøy ◽  
Asbjørn Holmgren ◽  
Olaug K. Rødningen ◽  
Trine M. Haugsand ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Mild Intellectual Disability ◽  
Facial Dysmorphisms

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.

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

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.

scholarly journals Bi-allelic Loss-of-Function Mutations in the NPR-C Receptor Result in Enhanced Growth and Connective Tissue Abnormalities

2018 ◽  
Vol 103 (2) ◽  
pp. 288-295 ◽  
Author(s):  
Eveline Boudin ◽  
Tjeerd R. de Jong ◽  
Tim C.R. Prickett ◽  
Bruno Lapauw ◽  
Kaatje Toye ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Allelic Loss ◽  
Loss Of Function ◽  
Tissue Abnormalities

scholarly journals A de novo variant in CASK gene causing intellectual disability and brain hypoplasia: A Case Report and Literature Review

2021 ◽  
Author(s):  
Ying Zhang ◽  
Yanyan Nie ◽  
Yu Mu ◽  
Jie Zheng ◽  
Xiaowei Xu ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Mental Disorders ◽  
De Novo ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
De Novo Mutation ◽  
Loss Of Function ◽  
Bioinformatics Analyses ◽  
Whole Exome ◽  
De Novo Variant

Abstract Background：The pathogenic variation of CASK gene can cause CASK related mental disorders. The main clinical manifestations are microcephaly with pontine and cerebellar hypoplasia, X-linked mental disorders with or without nystagmus and FG syndrome. The main pathogenic mechanism is the loss of function of related protein caused by mutation. We reported a Chinese male newborn with a de novo variant in CASK gene. Case presentation：We present an 18-day-old baby with intellectual disability and brain hypoplasia. Whole-exome sequencing was performed, which detected a hemizygous missense mutation c.764G>A of CASK gene. The mutation changed the 255th amino acid from Arg to His. Software based bioinformatics analyses were conducted to infer its functional effect.Conclusions：In this paper, a de novo mutation of CASK gene was reported. Moreover, a detailed description of all the cases described in the literature is reported.CASK mutations cause a variety of clinical phenotypes. Its diagnosis is difficult due to the lack of typical clinical symptoms. Genetic testing should be performed as early as possible if this disease is suspected. This case provides an important reference for the diagnosis and treatment of future cases.

scholarly journals Gain of channel function and modified gating properties in TRPM3 mutants causing intellectual disability and epilepsy

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Evelien Van Hoeymissen ◽  
Katharina Held ◽  
Ana Cristina Nogueira Freitas ◽  
Annelies Janssens ◽  
Thomas Voets ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Epileptic Activity ◽  
Gene Encoding ◽  
Epileptic Encephalopathies ◽  
Channel Function ◽  
Functional Consequences ◽  
Altered Response ◽  
Voltage Sensor Domain ◽  
Higher Sensitivity

Developmental and epileptic encephalopathies (DEE) are a heterogeneous group of disorders characterized by epilepsy with comorbid intellectual disability. Recently, two de novo heterozygous mutations in the gene encoding TRPM3, a calcium permeable ion channel, were identified as the cause of DEE in eight probands, but the functional consequences of the mutations remained elusive. Here we demonstrate that both mutations (V990M and P1090Q) have distinct effects on TRPM3 gating, including increased basal activity, higher sensitivity to stimulation by the endogenous neurosteroid pregnenolone sulfate (PS) and heat, and altered response to ligand modulation. Most strikingly, the V990M mutation affected the gating of the non-canonical pore of TRPM3, resulting in large inward cation currents via the voltage sensor domain in response to PS stimulation. Taken together, these data indicate that the two DEE mutations in TRPM3 result in a profound gain of channel function, which may lie at the basis of epileptic activity and neurodevelopmental symptoms in the patients.

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