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

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.

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

European Journal of Human Genetics ◽

10.1038/ejhg.2015.211 ◽

2015 ◽

Vol 24 (6) ◽

pp. 838-843 ◽

Cited By ~ 15

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

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Improving Emotional Competence in Children With Autism Spectrum Disorder and Mild Intellectual Disability in Schools: A Preliminary Treatment Versus Waitlist Study

Behaviour Change ◽

10.1017/bec.2019.13 ◽

2019 ◽

Vol 36 (4) ◽

pp. 216-232 ◽

Cited By ~ 1

Author(s):

Belinda Ratcliffe ◽

Michelle Wong ◽

David Dossetor ◽

Susan Hayes

Keyword(s):

Mental Health ◽

Autism Spectrum Disorder ◽

Intellectual Disability ◽

Social Skills ◽

Emotional Competence ◽

Children With Autism ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Medium Effect ◽

Mild Intellectual Disability

AbstractThis pilot study evaluated the effectiveness of delivering a new cognitive behavioural intervention package ‘Emotion-Based Social Skills Training (EBSST) for Children with Autism Spectrum Disorder (ASD) and Mild Intellectual Disability (ASD + MID)’ in schools. Fourteen school counsellors nominated 75 children (aged 7–13 years) with ASD + MID to receive 16 sessions of EBSST in groups of 3–8 children in their schools. Parent and teacher pre-post ratings of emotional competence (Emotions Development Questionnaire), social skills (Social Skills Improvement System Rating Scales) and mental health (Developmental Behaviour Checklist) were collected. Forty-three children received 16 sessions of EBSST and 32 children were allocated to the 9-month waitlist control group. Teachers and parents also received six EBSST training sessions in separate groups at school. Significant improvements in parent and teacher ratings of emotional competence were found at posttreatment among children in the EBSST group relative to controls; however, the results were not significant after the Bonferroni adjustment. Small to medium effect sizes were found. No difference in untrained social skills or mental health was observed. This study provides preliminary support for the utility of EBSST in teaching emotional competence skills for children with ASD + MID in schools and provides valuable pilot data for future research.

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

Epilepsia Open ◽

10.1002/epi4.12339 ◽

2019 ◽

Vol 4 (3) ◽

pp. 476-481 ◽

Cited By ~ 4

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

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Association of temporal lobe epilepsy with gambling disorder in a patient with mild intellectual disability and autism spectrum disorder

Seizure ◽

10.1016/j.seizure.2019.03.023 ◽

2019 ◽

Vol 69 ◽

pp. 17-19

Author(s):

Sam Tromans ◽

Beate Diehl ◽

Reza Kiani

Keyword(s):

Autism Spectrum Disorder ◽

Intellectual Disability ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Gambling Disorder ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Mild Intellectual Disability

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

European Journal of Human Genetics ◽

10.1038/s41431-018-0184-5 ◽

2018 ◽

Vol 26 (9) ◽

pp. 1388-1391 ◽

Cited By ~ 2

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

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

Molecular Autism ◽

10.1186/s13229-019-0286-0 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 2

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.

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

10.1101/2020.09.09.20187104 ◽

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.

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Online education of students with mild intellectual disability and autism spectrum disorder during the COVID-19 pandemic

Interdyscyplinarne Konteksty Pedagogiki Specjalnej ◽

10.14746/ikps.2020.29.07 ◽

2020 ◽

pp. 149-171

Author(s):

Marzena Buchnat ◽

Aneta Wojciechowska

Keyword(s):

Autism Spectrum Disorder ◽

Intellectual Disability ◽

Distance Learning ◽

Online Education ◽

Everyday Life ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Mild Intellectual Disability ◽

The Everyday ◽

Education Of Students

The situation of the pandemic of SARS-CoV-2 virus that causes COVID-19 disease is a new and unknown situation for everyone, causing fear and uncertainty. It is also a situation that has led to numerous changes in the everyday life of many people, including students who had to adapt to the new reality of distance education from day to day. The paper concerns with the situation of online education of students with mild intellectual disability and autism spectrum disorder. It is an attempt to indicate the difficulties encountered by this group of students in the situation of distance learning from a perspective of both the student and the teacher. The paper also indicates the issues which should be considered in this education, the way of its adaptation to the possibilities of the discussed group of students, as well as elementswhich are really important in this education.

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

Human Genome Variation ◽

10.1038/s41439-020-0102-6 ◽

2020 ◽

Vol 7 (1) ◽

Cited By ~ 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.

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