De novo Mutations (DNMs) in Autism Spectrum Disorder (ASD): Pathway and Network Analysis

Alonso-González, Aitana; Rodríguez-Fontenla, Cristina; Carracedo, Ángel

doi:10.3389/fgene.2018.00406

Cited by 45 publications

(28 citation statements)

References 140 publications

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“…Embryonic development requires the proper function of thousands of genes in order for cells to proliferate and divide, differentiate, migrate long distances to their final destination, and communicate with one another appropriately. Disruption of protein function due to mutations of genes that are required for these processes during embryogenesis can lead to severe developmental defects and neurodevelopmental disorders such as intellectual disabilities (ID) or Autism spectrum disorder (ASD) (Alonso-Gonzalez et al, 2018;Chen et al, 2019;Kasherman et al, 2020;Lasser et al, 2018;Sierra-Arregui et al, 2020). Genetic mutations caused by rare copy number variants (CNVs), including deletions and duplications, have been associated with neurodevelopmental disorders to varying degrees (Blazejewski et al, 2018;Deshpande and Weiss, 2018;Jensen et al, 2018;Pizzo et al, 2019;Rylaarsdam and Guemez-Gamboa, 2019;Singh et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

16p12.1 deletion orthologs are expressed in motile neural crest cells and are important for regulating craniofacial development inXenopus laevis

Lasser

Murphy

et al. 2020

Preprint

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Copy number variants (CNVs) associated with neurodevelopmental disorders are characterized by extensive phenotypic heterogeneity. In particular, one CNV was identified in a subset of children clinically diagnosed with intellectual disabilities (ID) that results in a hemizygous deletion of multiple genes at chromosome 16p12.1. In addition to ID, individuals with this deletion display a variety of symptoms including microcephaly, seizures, cardiac defects, and growth retardation. Moreover, patients also manifest severe craniofacial abnormalities, such as micrognathia, cartilage malformation of the ears and nose, and facial asymmetries; however, the function of the genes within the 16p12.1 region have not been studied in the context of vertebrate craniofacial development. The craniofacial tissues affected in patients with this deletion all derive from the same embryonic precursor, the cranial neural crest, leading to the hypothesis that one or more of the 16p12.1 genes may be involved in regulating neural crest cell (NCC)-related processes. To examine this, we characterized the developmental role of the 16p12.1-affected gene orthologs, polr3e, mosmo, uqcrc2, and cdr2, during craniofacial morphogenesis in the vertebrate model system, Xenopus laevis. While the currently-known cellular functions of these genes are diverse, we find that they share similar expression patterns along the neural tube, pharyngeal arches, and later craniofacial structures. As these genes show co-expression in the pharyngeal arches where NCCs reside, we sought to elucidate the effect of individual gene depletion on craniofacial development and NCC migration. We find that reduction of several 16p12.1 genes significantly disrupts craniofacial and cartilage formation, pharyngeal arch migration, as well as NCC specification and motility. Thus, we have determined that some of these genes play an essential role during vertebrate craniofacial patterning by regulating specific processes during NCC development, which may be an underlying mechanism contributing to the craniofacial defects associated with the 16p12.1 deletion.

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Section: Introductionmentioning

confidence: 99%

16p12.1 deletion orthologs are expressed in motile neural crest cells and are important for regulating craniofacial development inXenopus laevis

Lasser

Murphy

et al. 2020

Preprint

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“…Whereas ASD has been etiologically linked to parent disinterest in the 1960s, today it is accepted as a neurologic disorder [2]. Many studies have been conducted in recent years about the genetics of ASD, and it has been demonstrated that ASD has a significant genetic basis [3], [4]. In addition, there are evidence that age of parents, antenatal, prenatal and environmental factors make a contribution to the development of ASD [8], [9], [10], [11], [12].…”

Section: Discussionmentioning

confidence: 99%

“…ASD has been thought to be developed by parental disinterest in the first years of its definition, and it has been understood to be a neurobiological disorder in the following years [2]. Also, recent studies have found many genetic disorders about ASD, and it has been found that ASD has a genetic basis [3], [4].…”

Section: Introductionmentioning

confidence: 99%

Family Physicians' Awareness of Autism Spectrum Disorder: Results from a Survey Study

Altay

2019

Open Access Maced J Med Sci

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AIM: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder in children. Family physicians with the first medical contact of children are among the most frequent physicians with ASD. We aimed to investigate family physicians' awareness of ASD. METHODS: This study was carried out family physicians in between September 25-October 15, 2018. The questionnaire form on autism awareness prepared by the researcher was delivered to family physicians electronically and in printed form, and it was filled out by volunteers. RESULTS: Forty-eight family physicians with an average professional experience of 16.9 ± 8.8 years participated in the study. A group of 66.7% of the participants had not previously received education on ASD, and 70.8% of them did not refer any child to child psychiatry with suspected ASD in the last 6 months. The participants stated that the most common clinical features in children with ASD were the inability to make eye contact (72.9%) and repetitive movements (47.9%), and 56.3% of them stated one or more features that are not observed in ASD. The compliance of the participants' answers about the clinical features observed in children with ASD with the DSM-5 criteria was determined to be 54.6 ± 18.4%. Significantly higher compliance rates were observed in the participants with education on autism and those working as a physician below 15 years. CONCLUSION: In our study, family physicians' awareness of ASD was not found to be adequate. Education programs on autism awareness should be applied to family physicians who are probably the most frequently encountered physicians by children with ASD.

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“…and chromosomal alterations have also been associated with the development of the disorder [7,13,18,19].…”

Section: Aetiology Of Autism Spectrum Disordersmentioning

confidence: 99%

Experimental Models to Study Autism Spectrum Disorders: hiPSCs, Rodents and Zebrafish

Pensado‐López

Veiga-Rúa

Carracedo

et al. 2020

Genes

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Autism Spectrum Disorders (ASD) affect around 1.5% of the global population, which manifest alterations in communication and socialization, as well as repetitive behaviors or restricted interests. ASD is a complex disorder with known environmental and genetic contributors; however, ASD etiology is far from being clear. In the past decades, many efforts have been put into developing new models to study ASD, both in vitro and in vivo. These models have a lot of potential to help to validate some of the previously associated risk factors to the development of the disorder, and to test new potential therapies that help to alleviate ASD symptoms. The present review is focused on the recent advances towards the generation of models for the study of ASD, which would be a useful tool to decipher the bases of the disorder, as well as to conduct drug screenings that hopefully lead to the identification of useful compounds to help patients deal with the symptoms of ASD.

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De novo Mutations (DNMs) in Autism Spectrum Disorder (ASD): Pathway and Network Analysis

Cited by 45 publications

References 140 publications

16p12.1 deletion orthologs are expressed in motile neural crest cells and are important for regulating craniofacial development inXenopus laevis

16p12.1 deletion orthologs are expressed in motile neural crest cells and are important for regulating craniofacial development inXenopus laevis

Family Physicians' Awareness of Autism Spectrum Disorder: Results from a Survey Study

Experimental Models to Study Autism Spectrum Disorders: hiPSCs, Rodents and Zebrafish

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