Intellectual disability and autism spectrum disorders: Causal genes and molecular mechanisms

Srivastava, Anand; Schwartz, Charles E.

doi:10.1016/j.neubiorev.2014.02.015

Cited by 179 publications

(169 citation statements)

References 199 publications

(242 reference statements)

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“…Most known causes of severe ID are genetic, with about 25% of cases resulting from monogenic anomalies, copy-number variants and chromosomal abnormalities. 1,2 Efforts to identify causative genes implicated in monogenic forms of ID have produced multiple candidates, with a significant proportion of these genes (4100) mapping to the X chromosome. [3][4][5] In recent years, the implementation of highthroughput technologies, such as next-generation sequencing (NGS), array comparative genomic hybridization and single-nucleotide polymorphism (SNP) arrays, has facilitated and expedited the discovery of numerous genes that cause or contribute to various forms of ID.…”

Section: Introductionmentioning

confidence: 99%

Ten new cases further delineate the syndromic intellectual disability phenotype caused by mutations in DYRK1A

et al. 2015

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The dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) gene, located on chromosome 21q22.13 within the Down syndrome critical region, has been implicated in syndromic intellectual disability associated with Down syndrome and autism. DYRK1A has a critical role in brain growth and development primarily by regulating cell proliferation, neurogenesis, neuronal plasticity and survival. Several patients have been reported with chromosome 21 aberrations such as partial monosomy, involving multiple genes including DYRK1A. In addition, seven other individuals have been described with chromosomal rearrangements, intragenic deletions or truncating mutations that disrupt specifically DYRK1A. Most of these patients have microcephaly and all have significant intellectual disability. In the present study, we report 10 unrelated individuals with DYRK1A-associated intellectual disability (ID) who display a recurrent pattern of clinical manifestations including primary or acquired microcephaly, ID ranging from mild to severe, speech delay or absence, seizures, autism, motor delay, deep-set eyes, poor feeding and poor weight gain. We identified unique truncating and non-synonymous mutations (three nonsense, four frameshift and two missense) in DYRK1A in nine patients and a large chromosomal deletion that encompassed DYRK1A in one patient. On the basis of increasing identification of mutations in DYRK1A, we suggest that this gene be considered potentially causative in patients presenting with ID, primary or acquired microcephaly, feeding problems and absent or delayed speech with or without seizures.

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Section: Introductionmentioning

confidence: 99%

Ten new cases further delineate the syndromic intellectual disability phenotype caused by mutations in DYRK1A

et al. 2015

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“…Postorino and colleagues (2016), in a recent paper investigating the prevalence of ID and ASD in an Italian sample of children and adolescents, cited a number of studies which have found that there is a frequent co-occurrence between ID and ASD, and that both these disorders have been argued to share genetic substrates (e.g., Bolte & Poustka, 2002;Bonora et al, 2014;Charman et al, 2011;Deth, 2012;Fombonne, 2003Fombonne, , 2009Mefford, Batshaw, & Hoffman, 2012;Nicholl et al, 2014;Srivastava & Schwartz, 2014). Srivastava and Schwartz (2014) also suggest that these two disorders are significantly likely to be associated both biochemically and molecularly. Studies have found that as many as 70%…”

Section: Rates Of Overlap Between Intellectual Disability and Asdmentioning

confidence: 99%

“…Srivastava and Schwartz (2014) also suggest that these two disorders are significantly likely to be associated both biochemically and molecularly. Studies have found that as many as 70% of individuals with ASDs have some level of ID while the other 30% have some form of disability (e.g., speech, behavior) which is not cognitive dysfunction (Mefford et al, 2012;Newschaffer et al, 2007;Wilkins & Matson, 2009).…”

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confidence: 98%

A systematic PRISMA review of individuals with autism spectrum disorder in secure psychiatric care: prevalence, treatment, risk assessment and other clinical considerations

Allely

2018

JCP

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Purpose Patients with autism spectrum disorder (ASD) present with specific assessment, specific difficulties, needs and therapeutic issues and therefore are a challenging group for forensic services. Given the challenge that individuals with ASD present to forensic services, the suggested increase in the number of this group within this setting and the relatively little amount of research which suggests they face a number of difficulties within the prison environment, the purpose of this paper is to identify and review all the studies which have been carried out investigating any aspect of ASD in relation to secure hospital settings. Design/methodology/approach Seven internet-based bibliographic databases were used for the present review. The review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Findings A total of 12 studies were included in this review; 3 looked at the prevalence of ASD in secure psychiatric hospitals. One study evaluated the clinical utility of the AQ screening tool to assess self-reported autistic traits in secure psychiatric settings. Three explored any type of characteristics of patients with ASD detained in secure psychiatric hospitals. One study investigated the experiences or quality of life of patients with an ASD detained in secure psychiatric care. Two studies investigated awareness, knowledge and/or views regarding patients with ASD held by staff working within secure psychiatric hospitals. Lastly, three studies (one of which was also included in the prevalence category above) looked at the effectiveness of interventions or treatment of patients with ASD in secure psychiatric hospitals. Clinical recommendations and future research directions are discussed. Originality/value To the author’s knowledge, this is the first review to explore what research has been carried out looking specifically at patients with ASD in relation to secure forensic settings.

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“…Synaptic vesicles store neurotransmitters such as gammaaminobutyric acid (GABA) and glutamate [32]. Alterations in neurotransmission and/or synaptic storage of neurotransmitters can trigger serious neurologic disorders, including ASD [33].…”

Section: Neurotransmitter Signalling and Implications In Asdmentioning

confidence: 99%

Emerging Clues and Altered Metabolic Findings in Autism: Breakthroughs and Prospects from Omics Studies

Mowafy¹

2016

Autism Open Access

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Autism spectrum disorder (ASD) is a pervasive broad-spectrum disorder that involves multifaceted delays in the development of many basic, social, and communication skills. The etiology of ASD is multifactorial and involves interplay among genetic, neurologic, hormonal, metabolic, immune-inflammatory, and environmental factors; which further complicate both the diagnosis and management in affected individuals. This review delineates the underpinnings of clinical challenges posed by ASD, like clinical heterogeneity of patient presentation, unresolved ASD genomic map and deficient drug therapy. Besides, it addresses the emerging pathogenic, etiologic, and diagnostic clues of diverse origins, encompassing genetic-, neurotransmitter-, androgenic-and immunoinflammatory-anomalies in ASD patients, as availed by advances in Omics technologies (like genomics and proteomics). Moreover, as unravelled by metabolomics studies, metabolic flaws that pertain to amino acids, fatty acids, mitochondrial anomalies, and oxidative-stress are highlighted and further correlated with the extent of clinical picture and malbehaviors coherent with ASD patients. Lastly, future directions are underlined to promote and rationalize ASD research so as to help translate its findings into remedy.

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Intellectual disability and autism spectrum disorders: Causal genes and molecular mechanisms

Cited by 179 publications

References 199 publications

Ten new cases further delineate the syndromic intellectual disability phenotype caused by mutations in DYRK1A

Ten new cases further delineate the syndromic intellectual disability phenotype caused by mutations in DYRK1A

A systematic PRISMA review of individuals with autism spectrum disorder in secure psychiatric care: prevalence, treatment, risk assessment and other clinical considerations

Emerging Clues and Altered Metabolic Findings in Autism: Breakthroughs and Prospects from Omics Studies

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