1. Adi A, Tawil B, Aldosari M, Shinwari J, Nester M, Aldhalaan H, Alshamrani H, Ghannam M, Meyer B, Al Tassan N. {{Homozygosity analysis in subjects with autistic spectrum disorder}}. {Mol Med Rep};2015 (Apr 22)
Autistic spectrum disorder (ASD) is a complex neurodevelopmental disorder that results in social and communication impairments, as well as repetitive and stereotyped patterns. Genetically, ASD has been described as a multifactorial genetic disorder. The aim of the present study was to investigate possible susceptibility loci of ASD, utilizing the highly consanguineous and inbred nature of numerous families within the population of Saudi Arabia. A total of 13 multiplex families and 27 affected individuals were recruited and analyzed using Affymetrix GeneChip(R) Mapping 250K and 6.0 arrays as well as Axiom arrays. Numerous regions of homozygosity were identified, including regions in genes associated with synaptic function and neurotransmitters, as well as energy and mitochondriaassociated genes, and developmentallyassociated genes. The loci identified in the present study represent regions that may be further investigated, which could reveal novel changes and variations associated with ASD, reinforcing the complex inheritance of the disease.
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2. Benson R, Pinnaro C. {{Autonomy and autism: who speaks for the adolescent patient?}}. {AMA J Ethics};2015;17(4):305-309.
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3. Bent S, Hendren RL. {{Complementary and alternative treatments for autism part 1: evidence-supported treatments}}. {AMA J Ethics};2015;17(4):369-374.
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4. Block P. {{The Emergent Landscape of Autistic Communities and Autistic Studies}}. {Cult Med Psychiatry};2015 (Apr 23)
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5. Bozzetti MP, Specchia V, Cattenoz P, Laneve P, Geusa A, Sahin HB, Di Tommaso S, Friscini A, Massari S, Diebold C, Giangrande A. {{The Drosophila Fragile X Mental Retardation Protein participates in the piRNA pathway}}. {J Cell Sci};2015 (Apr 23)
RNA metabolism controls multiple biological processes and a specific class of small RNAs, called piRNAs, act as genome guardians by silencing the expression of transposons and repetitive sequences in the gonads. Defects in the piRNA pathway affect genome integrity and fertility. The possible implications in physiopathological mechanisms of human diseases have made the piRNA pathway the object of intense investigation and recent work calls for a role of this pathway in somatic processes including synaptic plasticity. The RNA-binding Fragile X Mental Retardation Protein (FMRP) controls translation and its loss triggers the most frequent syndromic form of mental retardation as well as gonadal defects in humans. We here demonstrate for the first time that germline as well as somatic expression of dFmr1, the Drosophila ortholog of FMRP, are necessary in a pathway mediated by piRNAs. Moreover, dFmr1 interacts genetically and biochemically with Aubergine, an Argonaute protein and a key player in this pathway. Our data open novel perspectives for understanding the phenotypes observed in Fragile X patients and support the view that piRNAs may be at work in the nervous system.
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6. Brosco JP. {{Conflicts in family-centered pediatric care for patients with autism}}. {AMA J Ethics};2015;17(4):299-304.
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7. Chien YL, Gau SS, Shang CY, Chiu YN, Tsai WC, Wu YY. {{Visual memory and sustained attention impairment in youths with autism spectrum disorders}}. {Psychol Med};2015 (Apr 23):1-11.
BACKGROUND: An uneven neurocognitive profile is a hallmark of autism spectrum disorder (ASD). Studies focusing on the visual memory performance in ASD have shown controversial results. We investigated visual memory and sustained attention in youths with ASD and typically developing (TD) youths. METHOD: We recruited 143 pairs of youths with ASD (males 93.7%; mean age 13.1, s.d. 3.5 years) and age- and sex-matched TD youths. The ASD group consisted of 67 youths with autistic disorder (autism) and 76 with Asperger’s disorder (AS) based on the DSM-IV criteria. They were assessed using the Cambridge Neuropsychological Test Automated Battery involving the visual memory [spatial recognition memory (SRM), delayed matching to sample (DMS), paired associates learning (PAL)] and sustained attention (rapid visual information processing; RVP). RESULTS: Youths with ASD performed significantly worse than TD youths on most of the tasks; the significance disappeared in the superior intelligence quotient (IQ) subgroup. The response latency on the tasks did not differ between the ASD and TD groups. Age had significant main effects on SRM, DMS, RVP and part of PAL tasks and had an interaction with diagnosis in DMS and RVP performance. There was no significant difference between autism and AS on visual tasks. CONCLUSIONS: Our findings implied that youths with ASD had a wide range of visual memory and sustained attention impairment that was moderated by age and IQ, which supports temporal and frontal lobe dysfunction in ASD. The lack of difference between autism and AS implies that visual memory and sustained attention cannot distinguish these two ASD subtypes, which supports DSM-5 ASD criteria.
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8. Engman ML, Sundin M, Miniscalco C, Westerlund J, Lewensohn-Fuchs I, Gillberg C, Fernell E. {{Prenatal acquired cytomegalovirus infection should be considered in children with autism}}. {Acta Paediatr};2015 (Apr 21)
AIM: The aim of the study was to evaluate the prevalence of congenital cytomegalovirus infection (CMV) in a representative sample of children with autism spectrum disorder. METHODS: In a representative group of 115 preschool children with autism spectrum disorder, of whom 33 also had intellectual disability, the dried blood spots from the newborn metabolic screening were analysed for CMV DNA using TaqMan-polymerase chain reaction. RESULTS: One of the 33 children with autism spectrum disorder and intellectual disability – 3% of that group – had congenital CMV infection. The corresponding prevalence in newborn infants in Sweden is 0.2%. None of the 82 children without intellectual disability had congenital CMV. CONCLUSION: The finding lends some further support for congenital CMV being one of the many aetiologies underlying autism spectrum disorder with intellectual disability. The rate of 3% of congenital CMV in children with autism spectrum disorder with intellectual disability has implications for the medical work-up. The finding of congenital CMV also indicates the need for repeated hearing assessments in the child. There is a need for similar studies with much larger samples. This article is protected by copyright. All rights reserved.
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9. Eshraghi AA, Nazarian R, Telischi FF, Martinez D, Hodges A, Velandia S, Cejas-Cruz I, Balkany TJ, Lo K, Lang D. {{Cochlear Implantation in Children With Autism Spectrum Disorder}}. {Otol Neurotol};2015 (Apr 20)
OBJECTIVE: To assess the outcome of cochlear implantation in children with autism spectrum disorder (ASD). STUDY DESIGN: Retrospective case review and survey. SETTING: Tertiary referral center. PATIENTS: Children who meet criteria for cochlear implantation and diagnosis of ASD. MAIN OUTCOME MEASURES: Receptive and expressive language scores and parental survey data. RESULTS: Fifteen patients with history of ASD and cochlear implantation were analyzed and compared with 15 patients who received cochlear implant and have no other disability. Postoperatively, more than 67% of children with ASD significantly improved their speech perception skills, and 60% significantly improved their speech expression skills, whereas all patients in the control group showed significant improvement in both aspects. The top 3 reported improvements after cochlear implantation were name recognition, response to verbal requests, and enjoyment of music. Of all behavioral aspects, the use of eye contact was the least improved. Survey results in regard to improvements in patient interaction were more subtle when compared with those related to sound and speech perception. The most improved aspects in the ASD patients’ lives after cochlear implantation seemed to be attending to other people’s requests and conforming to family routines. Of note, awareness of the child’s environment is the most highly ranked improvement attributed to the cochlear implant. CONCLUSION: Cochlear implants are effective and beneficial for hearing impaired members of the ASD population, although development of language may lag behind that of implanted children with no additional disabilities. Significant speech perception and overall behavior improvement are noted.
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10. Fortunato-Tavares T, Andrade CR, Befi-Lopes D, Limongi SO, Fernandes FD, Schwartz RG. {{Syntactic comprehension and working memory in children with specific language impairment, autism or Down syndrome}}. {Clin Linguist Phon};2015 (Apr 22):1-24.
This study examined syntactic assignment for predicates and reflexives as well as working memory effects in the sentence comprehension of children with Specific Language Impairment (SLI), Down syndrome (DS), high functioning Autism (HFA) and Typical Language Development (TLD). Fifty-seven children (35 boys and 22 girls) performed a computerised picture-selection sentence comprehension task. Predicate attachment and reflexive antecedent assignment (with working memory manipulations) were investigated. The results showed that SLI, HFA and DS children exhibited poorer overall performance than TLD children. Children with SLI exhibited similar performance to the DS and HFA children only when working memory demands were higher. We conclude that children with SLI, HFA and DS differ from children with TLD in their comprehension of predicate and reflexive structures where the knowledge of syntactic assignment is required. Working memory manipulation had different effects on syntactic comprehension depending on language disorder. Intelligence was not an explanatory factor for the differences observed in performance.
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11. Gilani SZ, Tan DW, Russell-Smith SN, Maybery MT, Mian A, Eastwood PR, Shafait F, Goonewardene M, Whitehouse AJ. {{Sexually dimorphic facial features vary according to level of autistic-like traits in the general population}}. {J Neurodev Disord};2015;7(1):14.
BACKGROUND: In a recent study, Bejerot et al. observed that several physical features (including faces) of individuals with an autism spectrum disorder (ASD) were more androgynous than those of their typically developed counterparts, suggesting that ASD may be understood as a ‘gender defiant’ disorder. These findings are difficult to reconcile with the hypermasculinisation account, which proposes that ASD may be an exaggerated form of cognitive and biological masculinity. The current study extended these data by first identifying six facial features that best distinguished males and females from the general population and then examining these features in typically developing groups selected for high and low levels of autistic-like traits. METHODS: In study 1, three-dimensional (3D) facial images were collected from 208 young adult males and females recruited from the general population. Twenty-three facial distances were measured from these images and a gender classification and scoring algorithm was employed to identify a set of six facial features that most effectively distinguished male from female faces. In study 2, measurements of these six features were compared for groups of young adults selected for high (n = 46) or low (n = 66) levels of autistic-like traits. RESULTS: For each sex, four of the six sexually dimorphic facial distances significantly differentiated participants with high levels of autistic-like traits from those with low trait levels. All four features were less masculinised for high-trait males compared to low-trait males. Three of four features were less feminised for high-trait females compared to low-trait females. One feature was, however, not consistent with the general pattern of findings and was more feminised among females who reported more autistic-like traits. Based on the four significantly different facial distances for each sex, discriminant function analysis correctly classified 89.7% of the males and 88.9% of the females into their respective high- and low-trait groups. CONCLUSIONS: The current data provide support for Bejerot et al.’s androgyny account since males and females with high levels of autistic-like traits generally showed less sex-typical facial features than individuals with low levels of autistic-like traits.
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12. Gotham K, Brunwasser SM, Lord C. {{Depressive and anxiety symptom trajectories from school age through young adulthood in samples with autism spectrum disorder and developmental delay}}. {J Am Acad Child Adolesc Psychiatry};2015 (May);54(5):369-376 e363.
OBJECTIVE: The objectives of this study were to model growth in anxiety and depressive symptoms from late school age through young adulthood in individuals with autism spectrum disorder (ASD) and controls with developmental delay (DD), and to assess relationships among internalizing growth patterns, participant characteristics, baseline predictors, and distal outcomes. METHOD: Data were collected between ages 6 and 24 years in 165 participants (n = 109 with ASD; n = 56 with nonspectrum DD), most of whom received diagnostic evaluations in both childhood and early adulthood. Questionnaires were collected approximately every 3 to 6 months between ages 9 and 24 years. Parent-rated Child Behavior Checklist (CBCL), Adult Behavior Checklist (ABCL), and Developmental Behaviour Checklist anxiety- and depression-related subscale distributions were modeled with mixed-effects Poisson models, covarying diagnosis, age, verbal IQ (VIQ), gender, and significant 2- and 3-way interactions. RESULTS: Anxiety was positively associated with VIQ, and controlling for VIQ, both anxiety and depressive symptoms were greater in ASD than nonspectrum participants. Female gender predicted greater increases over time in anxiety and depressive symptoms for both diagnostic groups. Lower maternal education was associated with increasing internalizing symptoms in a subset of less verbal individuals with ASD. In exploratory post hoc analyses, internalizing symptoms were associated with poorer emotional regulation in school age, and with lower life satisfaction and greater social difficulties in early adulthood. CONCLUSION: Findings support previous claims that individuals with ASD are at particular risk for affect- and anxiety-specific problems. Although symptom levels in females increase at a faster rate throughout adolescence, males with ASD appear to have elevated levels of depressive symptoms in school age that are maintained into young adulthood.
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13. Graf WD. {{Communicating Concern about Early Signs of Autism to Parents}}. {AMA J Ethics};2015;17(4):310-317.
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14. Jang DH, Chae H, Kim M. {{Autistic and Rett-like features associated with 2q33.3-q34 interstitial deletion}}. {Am J Med Genet A};2015 (Apr 21)
We describe the fourth reported case of a de novo 2q33.3-q34 interstitial deletion and review the literature in attempt to identify relevant candidate genes. A 15-month-old female patient presented for evaluation with poor eye contact and developmental delay. She had microcephaly and mild dysmorphic features, such as downslanting palpebral fissures, high forehead, small mouth, high palate, and general hypotonia. At 30 months of age, she was referred to the genetic clinic for an evaluation of persistent developmental delay, autistic traits, and Rett-like features, including bruxism and repetitive movement of the left hand. Chromosome analysis revealed 46,XX at the 550 band level. No abnormalities were found on analysis of MECP2 gene for Rett syndrome and a DNA methylation test for Prader-Willi syndrome. An array comparative genomic hybridization analysis revealed a de novo 2q33.3-q34 heterozygous deletion (206,048,173-211,980,867). The deletion was estimated to be 5.9 Mb in size and contained 34 known genes. Candidate genes were identified as NRP2, ADAM23, KLF7, CREB1, MAP2, UNC80, and LANCL1 for the 2q33.3-q34 interstitial deletion. (c) 2015 Wiley Periodicals, Inc.
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15. Kelly AM. {{Caring for Patients with ASD and Their Caregivers: Federal and State Autism-Specific Insurance Reform}}. {AMA J Ethics};2015;17(4):328-341.
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16. Lee BH, Smith T, Paciorkowski AR. {{Autism spectrum disorder and epilepsy: Disorders with a shared biology}}. {Epilepsy Behav};2015 (Apr 18)
There is an increasing recognition of clinical overlap in patients presenting with epilepsy and autism spectrum disorder (ASD), and a great deal of new information regarding the genetic causes of both disorders is available. Several biological pathways appear to be involved in both disease processes, including gene transcription regulation, cellular growth, synaptic channel function, and maintenance of synaptic structure. We review several genetic disorders where ASD and epilepsy frequently co-occur, and we discuss the screening tools available for practicing neurologists and epileptologists to help determine which patients should be referred for formal ASD diagnostic evaluation. Finally, we make recommendations regarding the workflow of genetic diagnostic testing available for children with both ASD and epilepsy. This article is part of a Special Issue entitled « Autism and Epilepsy ».
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17. Liu YF, Sowell SM, Luo Y, Chaubey A, Cameron RS, Kim HG, Srivastava AK. {{Autism and Intellectual Disability-Associated KIRREL3 Interacts with Neuronal Proteins MAP1B and MYO16 with Potential Roles in Neurodevelopment}}. {PLoS One};2015;10(4):e0123106.
Cell-adhesion molecules of the immunoglobulin superfamily play critical roles in brain development, as well as in maintaining synaptic plasticity, the dysfunction of which is known to cause cognitive impairment. Recently dysfunction of KIRREL3, a synaptic molecule of the immunoglobulin superfamily, has been implicated in several neurodevelopmental conditions including intellectual disability, autism spectrum disorder, and in the neurocognitive delay associated with Jacobsen syndrome. However, the molecular mechanisms of its physiological actions remain largely unknown. Using a yeast two-hybrid screen, we found that the KIRREL3 extracellular domain interacts with brain expressed proteins MAP1B and MYO16 and its intracellular domain can potentially interact with ATP1B1, UFC1, and SHMT2. The interactions were confirmed by co-immunoprecipitation and colocalization analyses of proteins expressed in human embryonic kidney cells, mouse neuronal cells, and rat primary neuronal cells. Furthermore, we show KIRREL3 colocalization with the marker for the Golgi apparatus and synaptic vesicles. Previously, we have shown that KIRREL3 interacts with the X-linked intellectual disability associated synaptic scaffolding protein CASK through its cytoplasmic domain. In addition, we found a genomic deletion encompassing MAP1B in one patient with intellectual disability, microcephaly and seizures and deletions encompassing MYO16 in two unrelated patients with intellectual disability, autism and microcephaly. MAP1B has been previously implicated in synaptogenesis and is involved in the development of the actin-based membrane skeleton. MYO16 is expressed in hippocampal neurons and also indirectly affects actin cytoskeleton through its interaction with WAVE1 complex. We speculate KIRREL3 interacting proteins are potential candidates for intellectual disability and autism spectrum disorder. Moreover, our findings provide further insight into understanding the molecular mechanisms underlying the physiological action of KIRREL3 and its role in neurodevelopment.
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18. Machado CO, Griesi-Oliveira K, Rosenberg C, Kok F, Martins S, Rita Passos-Bueno M, Sertie AL. {{Collybistin binds and inhibits mTORC1 signaling: a potential novel mechanism contributing to intellectual disability and autism}}. {Eur J Hum Genet};2015 (Apr 22)
Protein synthesis regulation via mammalian target of rapamycin complex 1 (mTORC1) signaling pathway has key roles in neural development and function, and its dysregulation is involved in neurodevelopmental disorders associated with autism and intellectual disability. mTOR regulates assembly of the translation initiation machinery by interacting with the eukaryotic initiation factor eIF3 complex and by controlling phosphorylation of key translational regulators. Collybistin (CB), a neuron-specific Rho-GEF responsible for X-linked intellectual disability with epilepsy, also interacts with eIF3, and its binding partner gephyrin associates with mTOR. Therefore, we hypothesized that CB also binds mTOR and affects mTORC1 signaling activity in neuronal cells. Here, by using induced pluripotent stem cell-derived neural progenitor cells from a male patient with a deletion of entire CB gene and from control individuals, as well as a heterologous expression system, we describe that CB physically interacts with mTOR and inhibits mTORC1 signaling pathway and protein synthesis. These findings suggest that disinhibited mTORC1 signaling may also contribute to the pathological process in patients with loss-of-function variants in CB.European Journal of Human Genetics advance online publication, 22 April 2015; doi:10.1038/ejhg.2015.69.
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19. Major NE. {{Autism education in residency training programs}}. {AMA J Ethics};2015;17(4):318-322.
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20. Mullin J. {{Drawing autism: showcasing the artistic talents of people with autism}}. {AMA J Ethics};2015;17(4):359-361.
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21. Parsi K, Elster N. {{A Life of One’s Own: Challenges in the Transition from Childhood to Adulthood with Autism Spectrum Disorder}}. {AMA J Ethics};2015;17(4):342-347.
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22. Rollins PR, Campbell M, Hoffman RT, Self K. {{A community-based early intervention program for toddlers with autism spectrum disorders}}. {Autism};2015 (Apr 23)
This study examined Pathways Early Autism Intervention, a community-based, parent-mediated, intensive behavioral and developmental intervention program for children with autism spectrum disorders that could be used as a model for state-funded early intervention programs. A single-subject, multiple-baseline, across-participants design was used. Four boys with autism spectrum disorder and their mothers participated. Interventionists made weekly home visits and worked with caregivers to establish and maintain face-to-face reciprocal social interaction and eye contact. Each session included a 10-min video of parent-child interaction. Evidence of intervention effectiveness was measured by percentage of nonoverlapping data points. Social validity was measured using questionnaire items in regard to parents’ perception of the intervention. The intervention was effective for the measures of eye contact, social engagement, and verbal reciprocity but not for nonverbal turn taking. Parents perceived the intervention as beneficial and easy to learn and incorporate into daily life.
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23. Rysavy MA, Murph JR. {{On Risks and Reality: Communicating the Difference between Autism Risks and Diagnosis}}. {AMA J Ethics};2015;17(4):323-327.
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24. Singer A, Ravi R. {{Complementary and alternative treatments for autism part 2: identifying and avoiding non-evidence-based treatments}}. {AMA J Ethics};2015;17(4):375-380.
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25. Svoboda DJ, Hosseini K, Schneider N, Casanova E, Aitch K. {{Artwork by people with autism}}. {AMA J Ethics};2015;17(4):362-368.
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26. Thurman AJ, McDuffie A, Kover ST, Hagerman RJ, Abbeduto L. {{Autism Symptomatology in Boys with Fragile X Syndrome: A Cross Sectional Developmental Trajectories Comparison with Nonsyndromic Autism Spectrum Disorder}}. {J Autism Dev Disord};2015 (Apr 23)
Although males with fragile X syndrome (FXS) are frequently described as demonstrating autism symptomatology, there is much debate regarding whether the behavioral symptoms representing the core domains of autism are the result of the same or different underlying neurological/psychological mechanisms. The present study used a cross-sectional developmental trajectories approach to compare the profiles of autism symptomatology relative to chronological age (CA), nonverbal IQ, and expressive vocabulary ability between individuals with FXS and individuals with nonsyndromic ASD. Results suggest that the onset of autism symptoms and their developmental trajectories in males with FXS differ in important ways as a function of CA, nonverbal cognitive ability, and expressive vocabulary relative to males with nonsyndromic ASD. Theoretical and clinical implications are discussed.
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27. Toma C, Torrico B, Hervas A, Salgado M, Rueda I, Valdes-Mas R, Buitelaar JK, Rommelse N, Franke B, Freitag C, Reif A, Perez-Jurado LA, Battaglia A, Mazzone L, Bacchelli E, Puente XS, Cormand B. {{Common and rare variants of microRNA genes in autism spectrum disorders}}. {World J Biol Psychiatry};2015 (Apr 23):1-11.
OBJECTIVES: MicroRNAs (miRNAs) are post-transcriptional regulators that have been shown to be involved in disease susceptibility. Here we explore the possible contribution of common and rare variants in miRNA genes in autism spectrum disorders (ASD). METHODS: A total of 350 tag SNPs from 163 miRNA genes were genotyped in 636 ASD cases and 673 controls. A replication study was performed in a sample of 449 ASD cases and 415 controls. Additionally, rare variants in 701 miRNA genes of 41 ASD patients were examined using whole-exome sequencing. RESULTS: The most significant association in the discovery sample was obtained for the miR-133b/miR-206 cluster (rs16882131, P = 0.00037). The replication study did not reach significance. However, the pooled analysis (1,085 cases and 1,088 controls) showed association with two miRNA clusters: miR-133b/miR-206 (rs16882131, permP = 0.037) and miR-17/miR-18a/miR-19a/miR-20a/miR-19b-1/miR92a-1 (rs6492538, permP = 0.019). Both miR-133b and miR-206 regulate the MET gene, previously associated with ASD. Rare variant analysis identified mutations in several miRNA genes, among them miR-541, a brain-specific miRNA that regulates SYN1, found mutated in ASD. CONCLUSIONS: Although our results do not establish a clear role for miRNAs in ASD, we pinpointed a few candidate genes. Further exome and GWAS studies are warranted to get more insight into their potential contribution to the disorder.
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28. Waltz MM. {{Mothers and autism: the evolution of a discourse of blame}}. {AMA J Ethics};2015;17(4):353-358.
