Dataset Information

SHANK1 Deletions in Males with Autism Spectrum Disorder.

ABSTRACT: Recent studies have highlighted the involvement of rare (<1% frequency) copy-number variations and point mutations in the genetic etiology of autism spectrum disorder (ASD); these variants particularly affect genes involved in the neuronal synaptic complex. The SHANK gene family consists of three members (SHANK1, SHANK2, and SHANK3), which encode scaffolding proteins required for the proper formation and function of neuronal synapses. Although SHANK2 and SHANK3 mutations have been implicated in ASD and intellectual disability, the involvement of SHANK1 is unknown. Here, we assess microarray data from 1,158 Canadian and 456 European individuals with ASD to discover microdeletions at the SHANK1 locus on chromosome 19. We identify a hemizygous SHANK1 deletion that segregates in a four-generation family in which male carriers--but not female carriers--have ASD with higher functioning. A de novo SHANK1 deletion was also detected in an unrelated male individual with ASD with higher functioning, and no equivalent SHANK1 mutations were found in >15,000 controls (p = 0.009). The discovery of apparent reduced penetrance of ASD in females bearing inherited autosomal SHANK1 deletions provides a possible contributory model for the male gender bias in autism. The data are also informative for clinical-genetics interpretations of both inherited and sporadic forms of ASD involving SHANK1.

SUBMITTER: Sato D

PROVIDER: S-EPMC3376495 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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SHANK1 Deletions in Males with Autism Spectrum Disorder.

Sato Daisuke D Lionel Anath C AC Leblond Claire S CS Prasad Aparna A Pinto Dalila D Walker Susan S O'Connor Irene I Russell Carolyn C Drmic Irene E IE Hamdan Fadi F FF Michaud Jacques L JL Endris Volker V Roeth Ralph R Delorme Richard R Huguet Guillaume G Leboyer Marion M Rastam Maria M Gillberg Christopher C Lathrop Mark M Stavropoulos Dimitri J DJ Anagnostou Evdokia E Weksberg Rosanna R Fombonne Eric E Zwaigenbaum Lonnie L Fernandez Bridget A BA Roberts Wendy W Rappold Gudrun A GA Marshall Christian R CR Bourgeron Thomas T Szatmari Peter P Scherer Stephen W SW

American journal of human genetics 20120412 5

Recent studies have highlighted the involvement of rare (<1% frequency) copy-number variations and point mutations in the genetic etiology of autism spectrum disorder (ASD); these variants particularly affect genes involved in the neuronal synaptic complex. The SHANK gene family consists of three members (SHANK1, SHANK2, and SHANK3), which encode scaffolding proteins required for the proper formation and function of neuronal synapses. Although SHANK2 and SHANK3 mutations have been implicated in ...[more]

PMID: 22503632

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Project description:BackgroundExisting research shows that adults with an autism spectrum disorder (ASD) are more vulnerable to develop overt psychosis. However, studies investigating (subclinical) psychotic experiences (PE) in ASD are scarce, and it is unknown if PE are accompanied with more distress in adults with ASD compared to the general population. This study examined lifetime PE and accompanying distress, momentary PE levels, and the impact of daily life stress and negative affect (NA) on momentary PE in males and females with ASD compared to controls.MethodsIn 50 adults with ASD (males N= 26, females N= 24) and 51 adults without ASD (males N= 26, females N= 25), the Community Assessment of Psychic Experiences (CAPE) was used to analyze group differences in frequency and distress of lifetime subclinical positive, negative, and depressive symptoms. The Experience Sampling Method (ESM) was used to measure momentary PE, NA, and stress (activity-related, event-related, and social stress) for 10 days. Multilevel analyses were conducted to test whether stress and NA were associated with momentary PE and whether these associations were modified by group or sex.ResultsAdults with ASD reported more lifetime CAPE negative and depressive symptoms, but similar levels of PE, than controls. Higher levels of accompanying distress were found in participants with ASD for each subscale. With respect to ESM momentary PE, higher levels were reported by adults with ASD and a stronger association between event-related stress and momentary PE was found compared to controls. This was not the case for NA, activity-related, and social stress. Overall, no significant differences between male and female outcomes were found.ConclusionAdults with ASD are more prone to encounter lifetime subclinical negative and depressive symptoms and accompanying distress compared to adults without ASD. Similar levels of lifetime PE in both groups were still accompanied with more distress in the ASD group. Furthermore, higher levels of ESM momentary PE were found in participants with ASD. Additionally, event-related stress may act as a risk factor for PE in both females and males with ASD, with a stronger risk-increasing effect than in their control counterparts.

Dataset Information

SHANK1 Deletions in Males with Autism Spectrum Disorder.

Publications

SHANK1 Deletions in Males with Autism Spectrum Disorder.

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