SHANK1 Deletions in Males with Autism Spectrum Disorder

Sato, Daisuke; Lionel, Anath C.; Leblond, Claire S.; Prasad, Aparna; Pinto, Dalila; Walker, Susan; O’Connor, Irene; Russell, Carolyn; Drmic, Irene; Hamdan, Fadi F.; Michaud, Jacques L.; Endris, Volker; Roeth, Ralph; Delorme, Richard; Huguet, Guillaume; Leboyer, Marion; Råstam, Maria; Gillberg, Christopher; Lathrop, Mark; Stavropoulos, Dimitri J.; Anagnostou, Evdokia; Weksberg, Rosanna; Fombonne, Éric; Zwaigenbaum, Lonnie; Fernandez, Bridget A.; Roberts, Wendy; Rappold, Gudrun; Marshall, Christian R.; Bourgeron, Thomas; Szatmári, Péter; Scherer, Stephen W.

doi:10.1016/j.ajhg.2012.03.017

Cited by 290 publications

(258 citation statements)

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“…Several de novo (non-inherited) mutations, such as those in the SHANK gene family [16] and the NRXN gene family [17], have been associated with ASD. However, mutations in these areas are also associated with other developmental disorders and so do not necessarily represent a unique genetic pathway to ASD [18,19].…”

Section: The Female Protective Effect: Genetic and Environmental Riskmentioning

confidence: 99%

Protective Effect or Missed Diagnosis? Females with Autism Spectrum Disorder

Hull

Mandy

2017

Future Neurol.

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Autism Spectrum Disorder (ASD) has historically been diagnosed more frequently in males than females. One explanation for this is the 'female protective effect': that there is something inherent in being female that makes girls and women less susceptible to ASD.Another possibility is that ASD is under-diagnosed in girls and women, due to the existence of a 'female autism phenotype', which is not well captured by current, male-biased diagnostic criteria. To evaluate the 'female protective effect' and 'female autism phenotype' hypotheses, this narrative review describes recent developments exploring the genetic underpinning and behavioural expression of ASD in females. We then look at ways to better identify females with ASD who may be missed under the current diagnostic criteria. KeywordsAutism, Autism Spectrum Disorders, Gender Differences, Sex Differences, Genetics, Diagnosis, Person-Environment Fit IntroductionAutism Spectrum Disorder (ASD) is a group of neurodevelopmental conditions characterised by deficits in social communication and reciprocity, and by restricted and repetitive interests and behaviours 1 . ASD is the current term used to integrate the previously separate diagnostic categories of autistic disorder, Asperger's disorder, childhood disintegrative disorder and pervasive developmental disorder -not otherwise specified (aka 'atypical autism' [2]). ASD is a lifelong condition that is present from birth. Although adult diagnosis is possible, symptoms must be reported as present from early developmental stages in order for the 1 In line with preferences from a majority of the autism community [1], we use identity-first language (e.g. 'autistic person') to refer to individuals with an ASD throughout this paper, while recognising that others might prefer person-first language (e.g. 'person with autism'). Gender differences in diagnosisASD affects approximately one to two per cent of the population [3,4], and is much more likely to be diagnosed in males than in females. Gender ratios in diagnosis vary depending on the country, cohort, and characteristics of those included, but average ratios are reported at around four males for every one female [3][4][5]. However, when looking at those individuals with intellectual disability, the male-to-female ratio narrows significantly to around two-toone [6]. In addition, population-based studies, which screen all participants in order to identify cases regardless of whether they have already been diagnosed by local services, suggest that the male-to-female ratio is closer to 3:1 [7,8]. This is in contrast to the average of around 4-5:1 generally reported in studies based on clinically-diagnosed cases [9]. The fact that a lower proportion of females are found in clinical samples than in community-based, epidemiological samples suggests that there is a bias against autistic girls and women coming to clinical attention. This bias may have existed from the very first conceptions of ASD; only 3 of 11 children in Kanner's original cases were female, and no gi...

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Section: The Female Protective Effect: Genetic and Environmental Riskmentioning

confidence: 99%

Protective Effect or Missed Diagnosis? Females with Autism Spectrum Disorder

Hull

Mandy

2017

Future Neurol.

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“…Within a few years, Shank2 was also identified as a risk gene [9,63], and these genetic findings were soon followed by the generation and analysis of transgenic mouse models. Shank1 was also investigated in mice as it has homology with Shank2/3, though it is also of interest in itself [64][65][66] and later, genetic variants were discovered as risk factors in patients [11].…”

Section: The Shank Family Of Proteinsmentioning

confidence: 99%

“…As genome-sequencing technology is evolving, large amounts of data continue to reveal de novo and inherited mutations of certain genes from ASD patients [8][9][10][11][12]. These sequencing studies are providing promising clues for investigating the cause of and finding potential therapeutics for autism and ASDs.…”

Section: Introductionmentioning

confidence: 99%

Shank mutant mice as an animal model of autism

Yoo

Bakes

Bradley

et al. 2014

Phil. Trans. R. Soc. B

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In this review, we focus on the role of the Shank family of proteins in autism. In recent years, autism research has been flourishing. With genetic, molecular, imaging and electrophysiological studies being supported by behavioural studies using animal models, there is real hope that we may soon understand the fundamental pathology of autism. There is also genuine potential to develop a molecular-level pharmacological treatment that may be able to deal with the most severe symptoms of autism, and clinical trials are already underway. The Shank family of proteins has been strongly implicated as a contributing factor in autism in certain individuals and sits at the core of the alleged autistic pathway. Here, we analyse studies that relate Shank to autism and discuss what light this sheds on the possible causes of autism.

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“…Some CNVs identified in large case-control studies consist of only 1 or a few genes. These include deletions in 1p33 (AGBL4) [104], 2p16.3 (NRXN1) [106], 3p26.2 (SUMF1) [106], 10q23.2 (GRID1) [106], 19q13.33 (CLEC11A, SHANK1, SYT3) [166], and Xp22.1 (DDX53, PTCHD1) [104], as well as duplications in 3p26.3 (CNTN4) [106] and 3q26.31 (NLGN1) [106]. Among the most highly recurrent single-gene CNVs are NRXN1 mutations.…”

Section: Other Recurrent Cnvs In Asd and Cnvs That Identify Individuamentioning

confidence: 99%

Discovery of Rare Mutations in Autism: Elucidating Neurodevelopmental Mechanisms

et al. 2015

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Autism spectrum disorder (ASD) is a group of highly genetic neurodevelopmental disorders characterized by language, social, cognitive, and behavioral abnormalities. ASD is a complex disorder with a heterogeneous etiology. The genetic architecture of autism is such that a variety of different rare mutations have been discovered, including rare monogenic conditions that involve autistic symptoms. Also, de novo copy number variants and single nucleotide variants contribute to disease susceptibility. Finally, autosomal recessive loci are contributing to our understanding of inherited factors. We will review the progress that the field has made in the discovery of these rare genetic variants in autism. We argue that mutation discovery of this sort offers an important opportunity to identify neurodevelopmental mechanisms in disease. The hope is that these mechanisms will show some degree of convergence that may be amenable to treatment intervention.

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SHANK1 Deletions in Males with Autism Spectrum Disorder

Cited by 290 publications

References 50 publications

Protective Effect or Missed Diagnosis? Females with Autism Spectrum Disorder

Protective Effect or Missed Diagnosis? Females with Autism Spectrum Disorder

Shank mutant mice as an animal model of autism

Discovery of Rare Mutations in Autism: Elucidating Neurodevelopmental Mechanisms

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