scholarly journals De novo variants in SETD1B cause intellectual disability, autism spectrum disorder, and epilepsy with myoclonic absences

2019 ◽  
Vol 4 (3) ◽  
pp. 476-481 ◽  
Author(s):  
Takuya Hiraide ◽  
Ayako Hattori ◽  
Daisuke Ieda ◽  
Ikumi Hori ◽  
Shinji Saitoh ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Intellectual Disability ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder

scholarly journals A de novo microdeletion of SEMA5A in a boy with autism spectrum disorder and intellectual disability

2015 ◽  
Vol 24 (6) ◽  
pp. 838-843 ◽  
Author(s):  
Anne-Laure Mosca-Boidron ◽  
Lucie Gueneau ◽  
Guillaume Huguet ◽  
Alice Goldenberg ◽  
Céline Henry ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Intellectual Disability ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder

scholarly journals A 9-year-old-girl with Phelan McDermid Syndrome, who had been diagnosed with an autism spectrum disorder

2016 ◽  
Vol 19 (2) ◽  
pp. 85-90 ◽  
Author(s):  
I Görker ◽  
H Gürkan ◽  
S Demir Ulusal ◽  
E Atlı ◽  
E Ikbal Atlı
Keyword(s):  
Autism Spectrum Disorder ◽  
Intellectual Disability ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Comparative Genomic ◽  
Parental Origin ◽  
Mild Intellectual Disability ◽  
First Case

AbstractPhelan McDermid Syndrome (PHMDS) (OMIM #606232), is a contiguous gene disorder resulting from deletion of the distal long arm of chromosome 22. The 22q13.3 deletions and mutations that lead to a loss of a functional copy of SHANK3 (OMIM *606230) cause the syndrome, characterized by moderate to profound intellectual disability, severely delayed or absent speech, hypotonia, and autism spectrum disorder (ASD) or ASD traits. In this study, we present the case of a 9-year-old girl who had earlier been diagnosed with an ASD. Our findings were a clinically mild intellectual disability, rounded face, pointed chin but no autistic findings. We learned that her neuromotor development was delayed and she had neonatal hypotonia in her history. A heterozygous deletion of MLC1, SBF1, MAPK8IP2, ARSA, SHANK3 and ACR genes, located on 22q13.33, was defined by multiplex ligation-dependent probe amplification (MLPA). Deletion of 22q13.3 (ARSA) region was confirmed by a fluorescent in situ hybridization (FISH) technique. The 22q13.3 deletion was found to be de novo in our patient, and she was diagnosed with PHMDS. We confirmed the 22q13.3 deletion and also determined a gain of 8p23.3-23.2 by array comparative genomic hybridization (aCGH). Fluorescent in situ hybridization was performed to determine whether the deletion was of parental origin and to identify regions of chromosomes where the extra 8p may have been located. The parents were found to be normal. The extra copy of 8p was observed on 22q in the patient. She is the first case reported in association with the 22q deletion of 8p duplications in the literature.

scholarly journals A recurrent de novo CUX2 missense variant associated with intellectual disability, seizures, and autism spectrum disorder

2018 ◽  
Vol 26 (9) ◽  
pp. 1388-1391 ◽  
Author(s):  
Maria Barington ◽  
Lotte Risom ◽  
Jakob Ek ◽  
Peter Uldall ◽  
Elsebet Ostergaard
Keyword(s):  
Autism Spectrum Disorder ◽  
Intellectual Disability ◽  
De Novo ◽  
Missense Variant ◽  
Autism Spectrum ◽  
Spectrum Disorder

scholarly journals Disruption of PHF21A causes syndromic intellectual disability with craniofacial anomalies, epilepsy, hypotonia, and neurobehavioral problems including autism

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Hyung-Goo Kim ◽  
Jill A. Rosenfeld ◽  
Daryl A. Scott ◽  
Gerard Bénédicte ◽  
Jonathan D. Labonne ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Intellectual Disability ◽  
Missense Mutation ◽  
De Novo ◽  
Fetal Brain ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Craniofacial Anomalies ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Region

Abstract Background PHF21A has been associated with intellectual disability and craniofacial anomalies based on its deletion in the Potocki-Shaffer syndrome region at 11p11.2 and its disruption in three patients with balanced translocations. In addition, three patients with de novo truncating mutations in PHF21A were reported recently. Here, we analyze genomic data from seven unrelated individuals with mutations in PHF21A and provide detailed clinical descriptions, further expanding the phenotype associated with PHF21A haploinsufficiency. Methods Diagnostic trio whole exome sequencing, Sanger sequencing, use of GeneMatcher, targeted gene panel sequencing, and MiSeq sequencing techniques were used to identify and confirm variants. RT-qPCR was used to measure the normal expression pattern of PHF21A in multiple human tissues including 13 different brain tissues. Protein-DNA modeling was performed to substantiate the pathogenicity of the missense mutation. Results We have identified seven heterozygous coding mutations, among which six are de novo (not maternal in one). Mutations include four frameshifts, one nonsense mutation in two patients, and one heterozygous missense mutation in the AT Hook domain, predicted to be deleterious and likely to cause loss of PHF21A function. We also found a new C-terminal domain composed of an intrinsically disordered region. This domain is truncated in six patients and thus likely to play an important role in the function of PHF21A, suggesting that haploinsufficiency is the likely underlying mechanism in the phenotype of seven patients. Our results extend the phenotypic spectrum of PHF21A mutations by adding autism spectrum disorder, epilepsy, hypotonia, and neurobehavioral problems. Furthermore, PHF21A is highly expressed in the human fetal brain, which is consistent with the neurodevelopmental phenotype. Conclusion Deleterious nonsense, frameshift, and missense mutations disrupting the AT Hook domain and/or an intrinsically disordered region in PHF21A were found to be associated with autism spectrum disorder, epilepsy, hypotonia, neurobehavioral problems, tapering fingers, clinodactyly, and syndactyly, in addition to intellectual disability and craniofacial anomalies. This suggests that PHF21A is involved in autism spectrum disorder and intellectual disability, and its haploinsufficiency causes a diverse neurological phenotype.

scholarly journals Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior

2020 ◽  
Author(s):  
Holly K. Harris ◽  
Tojo Nakayama ◽  
Jenny Lai ◽  
Boxun Zhao ◽  
Nikoleta Argyrou ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Attention Deficit Hyperactivity Disorder ◽  
Transcription Factors ◽  
Intellectual Disability ◽  
Attention Deficit ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Risk Genes ◽  
Hyperactivity Disorder

Purpose: We describe a novel neurobehavioral syndrome of autism spectrum disorder, intellectual disability, and attention deficit/hyperactivity disorder associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. Methods: We assembled a cohort of 36 individuals (from 31 unrelated families) with de novo mutations in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. Results: These individuals share neurobehavioral features including autism spectrum disorder (ASD), intellectual disability, and attention-deficit/hyperactivity disorder (ADHD); other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. Conclusion: These results establish deleterious variation in RFX3, RFX4, and RFX7 as important causes of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.

scholarly journals Tatton-Brown-Rahman syndrome with a novel DNMT3A mutation presented severe intellectual disability and autism spectrum disorder

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Takayuki Yokoi ◽  
Yumi Enomoto ◽  
Takuya Naruto ◽  
Kenji Kurosawa ◽  
Norimichi Higurashi
Keyword(s):  
Autism Spectrum Disorder ◽  
Intellectual Disability ◽  
Developmental Disorders ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
De Novo Mutation ◽  
Facial Features ◽  
Severe Intellectual Disability ◽  
Dominant Disease

AbstractTatton-Brown-Rahman syndrome is a congenital anomaly syndrome that manifests with overgrowth, macrocephaly, and characteristic facial features. This autosomal dominant disease is caused by a germline mutation in DNMT3A. Some patients with this syndrome develop mild to severe intellectual disability, which is sometimes accompanied by autism spectrum disorder or other developmental disorders. We report a Japanese patient with severe intellectual disability and autism spectrum disorder with a de novo mutation in the active domain of DNMT3A.

scholarly journals ZNF462 and KLF12 are disrupted by a de novo translocation in a patient with syndromic intellectual disability and autism spectrum disorder

2018 ◽  
Vol 61 (7) ◽  
pp. 376-383 ◽  
Author(s):  
Nele Cosemans ◽  
Laura Vandenhove ◽  
Jarymke Maljaars ◽  
Hilde Van Esch ◽  
Koenraad Devriendt ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Intellectual Disability ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
De Novo Translocation

scholarly journals Intranasal oxytocin administration ameliorates social behavioral deficits in a POGZWT/Q1038R mouse model of autism spectrum disorder

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Kohei Kitagawa ◽  
Kensuke Matsumura ◽  
Masayuki Baba ◽  
Momoka Kondo ◽  
Tomoya Takemoto ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Behavior ◽  
Mouse Model ◽  
Mouse Models ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
De Novo Mutation ◽  
Behavioral Deficits

AbstractAutism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by core symptoms of impaired social behavior and communication. Recent studies have suggested that the oxytocin system, which regulates social behavior in mammals, is potentially involved in ASD. Mouse models of ASD provide a useful system for understanding the associations between an impaired oxytocin system and social behavior deficits. However, limited studies have shown the involvement of the oxytocin system in the behavioral phenotypes in mouse models of ASD. We have previously demonstrated that a mouse model that carries the ASD patient-derived de novo mutation in the pogo transposable element derived with zinc finger domain (POGZWT/Q1038R mice), showed ASD-like social behavioral deficits. Here, we have explored whether oxytocin (OXT) administration improves impaired social behavior in POGZWT/Q1038R mice and found that intranasal oxytocin administration effectively restored the impaired social behavior in POGZWT/Q1038R mice. We also found that the expression level of the oxytocin receptor gene (OXTR) was low in POGZWT/Q1038R mice. However, we did not detect significant changes in the number of OXT-expressing neurons between the paraventricular nucleus of POGZWT/Q1038R mice and that of WT mice. A chromatin immunoprecipitation assay revealed that POGZ binds to the promoter region of OXTR and is involved in the transcriptional regulation of OXTR. In summary, our study demonstrate that the pathogenic mutation in the POGZ, a high-confidence ASD gene, impairs the oxytocin system and social behavior in mice, providing insights into the development of oxytocin-based therapeutics for ASD.

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