1. Adachi S, Torio M, Okuzono S, Motomura Y, Ichimiya Y, Sonoda Y, Nagata J, Okamoto M, Notomi S, Sanefuji M, Sakai Y, Ohga S. Vitamin A deficiency-associated corneal perforation in a boy with autism spectrum disorder: A case report and literature review. Nutrition (Burbank, Los Angeles County, Calif). 2021; 90: 111275.

BACKGROUND: Malnutrition and vitamin deficiency are growing concerns in the clinical management of children with autism spectrum disorder (ASD). This case report presents a boy with ASD who developed vitamin A deficiency during follow-up. CASE REPORT: A 7-y-old boy had been diagnosed with ASD and developmental delay at age 18 mo. He developed convulsions associated with hypocalcemia and vitamin D deficiency at 3 y of age. Although vitamin D supplementation was continued, he was only able to eat rice, green tea, and fried potatoes from 3 y of age to age 7 y. He had started rubbing his eyes and had refused to open his eyes 9 mo before. An ophthalmologic examination showed bilateral corneal ulcers and right corneal perforation. Vitamin A was immediately supplemented with a nasogastric tube; however, his right eye was surgically enucleated against the persistent infection. LITERATURE REVIEW: A search of the relevant literature from 1993 to 2020 identified 11 cases of patients with ASD (5-17 y of age) who developed vitamin A deficiency owing to malnutrition. Only 4 cases (36%) had a full recovery in visual acuity. CONCLUSION: Vitamin A deficiency frequently causes irreversible visual impairment in children with ASD. Vigilant monitoring of vitamin levels prevents unfavorable outcomes in children with ASD and difficulty in food intake.

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2. Barnhart AJ, Dierickx K. Cultures and cures: neurodiversity and brain organoids. BMC medical ethics. 2021; 22(1): 61.

BACKGROUND: Research with cerebral organoids is beginning to make significant progress in understanding the etiology of autism spectrum disorder (ASD). Brain organoid models can be grown from the cells of donors with ASD. Researchers can explore the genetic, developmental, and other factors that may give rise to the varieties of autism. Researchers could study all of these factors together with brain organoids grown from cells originating from ASD individuals. This makes brain organoids unique from other forms of ASD research. They are like a multi-tool, one with significant versatility for the scope of ASD research and clinical applications. There is hope that brain organoids could one day be used for precision medicine, like developing tailored ASD drug treatments. MAIN BODY: Brain organoid researchers often incorporate the medical model of disability when researching the origins of ASD, especially when the research has the specific aim of potentially finding tailored clinical treatments for ASD individuals. The neurodiversity movement-a developmental disability movement and paradigm that understands autism as a form of natural human diversity-will potentially disagree with approaches or aims of cerebral organoid research on ASD. Neurodiversity advocates incorporate a social model of disability into their movement, which focuses more on the social, attitudinal, and environmental barriers rather than biophysical or psychological deficits. Therefore, a potential conflict may arise between these perspectives on how to proceed with cerebral organoid research regarding neurodevelopmental conditions, especially ASD. CONCLUSIONS: Here, we present these perspectives and give at least three initial recommendations to achieve a more holistic and inclusive approach to cerebral organoid research on ASD. These three initial starting points can build bridges between researchers and the neurodiversity movement. First, neurodiverse individuals should be included as co-creators in both the scientific process and research communication. Second, clinicians and neurodiverse communities should have open and respectful communication. Finally, we suggest a continual reconceptualization of illness, impairment, disability, behavior, and person.

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3. Cederlund M. Parent Questionnaires in the Evaluation of Pre-School Children Referred for Neuropsychiatric Assessment. Journal of autism and developmental disorders. 2022; 52(4): 1742-51.

One-hundred twenty-four pre-school children referred for assessment to a neuropsychiatric team were included in this study of the Autism Behavior Checklist (ABC), ESSENCE-Q, and Conners Abbreviated Parent-Teacher Rating Scale (CAPRS). All three questionnaires showed a good correlation towards severity of symptoms in ASD. The ABC questionnaire was, as has been shown in earlier research less accurate in identifying individuals with ASD having an IQ within the normal range. However the ESSENCE-Q, and the CAPRS proved to identify children with difficulties needing further assessment regardless of intellectual ability. The CAPRS showed a good correlation to severity in ASD indicating difficulties in the regulation of activity and behavior likely to be connected to ASD in pre-school children.

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4. Chaplin E, McCarthy J, Allely CS, Forrester A, Underwood L, Hayward H, Sabet J, Young S, Mills R, Asherson P, Murphy D. Self-harm and Mental Health Characteristics of Prisoners with elevated rates of autistic traits. Research in developmental disabilities. 2021; 114: 103987.

BACKGROUND: Prevalence studies among prisoners have found rates of 1-4% for autism spectrum disorder (ASD) or autistic traits. However, little is known about those prisoners with high levels of autistic traits. AIM: This aim of this study was to compare the mental health characteristics of prisoners with autistic traits with neurotypical prisoners not screening positive for neurodevelopmental disorders. METHOD: The study recruited 240 male prisoners from a London prison and screened for autism spectrum disorder using the Autism Quotient (AQ) 20 and 10, and Autism Diagnostic Observation Schedule (ADOS). The Mini International Neuropsychiatric Interview was used to assess for depression, anxiety, self-harm behavior and suicide. RESULTS: Screening using the AQ identified 46 prisoners with significant autistic traits, with 12 meeting the diagnostic threshold for ASD using the ADOS. Those screening positive with autistic traits were significantly more likely to have thought about self-harm and suicide in the past month than neurotypical prisoners and have a comorbid mental disorder. They were also significantly more likely to report having attempted suicide during their lifetime compared to neurotypical peers at a rate of 64.9 % compared to 11.6 % for the neurotypical prisoners. CONCLUSION: Prisoners with elevated levels of autistic traits were more likely to report self-harm, suicidal thoughts and were more vulnerable to a range of mental disorders than neurotypical prisoners. There is a need for more evidence on the experience of autistic prisoners to inform how pathways should work to improve health outcomes through increased awareness and access to screening and subsequent diagnosis which currently prisons are currently not set up for.

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5. Daedelow LS, Beck A, Romund L, Mascarell-Maricic L, Dziobek I, Romanczuk-Seiferth N, Wüstenberg T, Heinz A. Neural correlates of RDoC-specific cognitive processes in a high-functional autistic patient: a statistically validated case report. Journal of neural transmission (Vienna, Austria : 1996). 2021; 128(6): 845-59.

The level of functioning of individuals with autism spectrum disorder (ASD) varies widely. To better understand the neurobiological mechanism associated with high-functioning ASD, we studied the rare case of a female patient with an exceptional professional career in the highly competitive academic field of Mathematics. According to the Research Domain Criteria (RDoC) approach, which proposes to describe the basic dimensions of functioning by integrating different levels of information, we conducted four fMRI experiments targeting the (1) social processes domain (Theory of mind (ToM) and face matching), (2) positive valence domain (reward processing), and (3) cognitive domain (N-back). Patient’s data were compared to data of 14 healthy controls (HC). Additionally, we assessed the subjective experience of our case during the experiments. The patient showed increased response times during face matching and achieved a higher total gain in the Reward task, whereas her performance in N-back and ToM was similar to HC. Her brain function differed mainly in the positive valence and cognitive domains. During reward processing, she showed reduced activity in a left-hemispheric frontal network and cortical midline structures but increased connectivity within this network. During the working memory task patients’ brain activity and connectivity in left-hemispheric temporo-frontal regions were elevated. In the ToM task, activity in posterior cingulate cortex and temporo-parietal junction was reduced. We suggest that the high level of functioning in our patient is rather related to the effects in brain connectivity than to local cortical information processing and that subjective report provides a fruitful framework for interpretation.

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6. Dudley B, Ostrowski M, Ciausu V, Ince C, McKinnon I. Revisiting vitamin D status and supplementation for in-patients with intellectual and developmental disability in the North of England, UK. BJPsych bulletin. 2021: 1-7.

AIMS AND METHOD: To re-evaluate vitamin D testing and supplementation among in-patients with intellectual and developmental disability (IDD) and examine any correlates with physical health conditions, including COVID-19. Records of all in-patients between January 2019 and July 2020 (n = 78) were examined for 25-hydroxyvitamin D (25(OH)D) level, ward area, supplementation status, test seasonality, medication and health status. RESULTS: The mean 25(OH)D level for supplemented (800 IU/day) patients was 75 nmol/L (s.d. = 20), compared with 40 nmol/L (s.d. = 19) in the non-supplemented group (P < 0.001). Thirty-eight percent of those who were in-patients during the first wave of the COVID-19 pandemic developed symptoms, but the small sample size could not establish vitamin D levels as a predictor of outcome. CLINICAL IMPLICATIONS: Vitamin D (800 IU/day) supplementation is effective but the adequacy of the nationally recommended dose of 400 IU/day is unclear. Links to COVID-19 merit further research.

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7. English MCW, Gignac GE, Visser TAW, Whitehouse AJO, Enns JT, Maybery MT. The Comprehensive Autistic Trait Inventory (CATI): development and validation of a new measure of autistic traits in the general population. Molecular autism. 2021; 12(1): 37.

BACKGROUND: Traits and characteristics qualitatively similar to those seen in diagnosed autism spectrum disorder can be found to varying degrees in the general population. To measure these traits and facilitate their use in autism research, several questionnaires have been developed that provide broad measures of autistic traits [e.g. Autism-Spectrum Quotient (AQ), Broad Autism Phenotype Questionnaire (BAPQ)]. However, since their development, our understanding of autism has grown considerably, and it is arguable that existing measures do not provide an ideal representation of the trait dimensions currently associated with autism. Our aim was to create a new measure of autistic traits that reflects our current understanding of autism, the Comprehensive Autism Trait Inventory (CATI). METHODS: In Study 1, 107 pilot items were administered to 1119 individuals in the general population and exploratory factor analysis of responses used to create the 42-item CATI comprising six subscales: Social Interactions, Communication, Social Camouflage, Repetitive Behaviours, Cognitive Rigidity, and Sensory Sensitivity. In Study 2, the CATI was administered to 1068 new individuals and confirmatory factor analysis used to verify the factor structure. The AQ and BAPQ were administered to validate the CATI, and additional autistic participants were recruited to compare the predictive ability of the measures. In Study 3, to validate the CATI subscales, the CATI was administered to 195 new individuals along with existing valid measures qualitatively similar to each CATI subscale. RESULTS: The CATI showed convergent validity at both the total-scale (r ≥ .79) and subscale level (r ≥ .68). The CATI also showed superior internal reliability for total-scale scores (α = .95) relative to the AQ (α = .90) and BAPQ (α = .94), consistently high reliability for subscales (α > .81), greater predictive ability for classifying autism (Youden’s Index = .62 vs .56-.59), and demonstrated measurement invariance for sex. LIMITATIONS: Analyses of predictive ability for classifying autism depended upon self-reported diagnosis or identification of autism. The autistic sample was not large enough to test measurement invariance of autism diagnosis. CONCLUSIONS: The CATI is a reliable and economical new measure that provides observations across a wide range of trait dimensions associated with autism, potentially precluding the need to administer multiple measures, and to our knowledge, the CATI is also the first broad measure of autistic traits to have dedicated subscales for social camouflage and sensory sensitivity.

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8. Feldman JI, Raj S, Bowman SM, Santapuram P, Golden AJ, Daly C, Dunham K, Suzman E, Augustine AE, Garla V, Muhumuza A, Cascio CJ, Williams KL, Kirby AV, Keceli-Kaysili B, Woynaroski TG. Sensory Responsiveness Is Linked With Communication in Infant Siblings of Children With and Without Autism. Journal of speech, language, and hearing research : JSLHR. 2021; 64(6): 1964-76.

Purpose Differences in communication development impact long-term outcomes of children with autism. Previous research has identified factors associated with communication in children with autism, but much of the variance in communication skill remains unexplained. It has been proposed that early differences in sensory responsiveness (i.e., hyporesponsiveness, hyperresponsiveness, and sensory seeking) may produce « cascading effects » on communication. Evidence for this theory is limited, however, as relations between sensory responsiveness and communication in the earliest stages of development have not been well established. The purpose of this study was to evaluate (a) whether infants with a heightened likelihood of autism diagnosis (i.e., infants with an older sibling with autism) differ from infants at general population-level likelihood of autism (i.e., infants with an older, nonautistic sibling) on patterns of sensory responsiveness, (b) whether early sensory responsiveness is correlated with concurrent communication, and (c) whether the aforementioned between-groups differences and associations are moderated by age. Method Participants were 40 infants (20 infants with an older sibling with autism, 20 infants with an older, nonautistic sibling) aged 12-18 months. A series of observational and parent report measures of sensory responsiveness and communication skill were administered. Results Group differences in sensory responsiveness across the 12- to 18-month period were limited (i.e., only observed for one measure of hyporesponsiveness), though selected differences in sensory responsiveness (i.e., parent-reported hyperresponsiveness and sensory seeking) emerged between groups over this developmental window. Parent-reported hyporesponsiveness was unconditionally, negatively associated with communication skills. Associations between expressive communication and (a) parent-reported sensory seeking and (b) an observational measure of hyperresponsiveness were moderated by age. Conclusions This study provides new insights into the nature of sensory responsiveness and theorized links with communication skill in infants at elevated and general population-level likelihood of autism diagnosis. Further work is needed to better characterize the effects of interest in a larger sample spanning a wider age range. Supplemental Material https://doi.org/10.23641/asha.14515542.

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9. Inoue T, Otani R, Iguchi T, Ishii R, Uchida S, Okada A, Kitayama S, Koyanagi K, Suzuki Y, Suzuki Y, Sumi Y, Takamiya S, Tsurumaru Y, Nagamitsu S, Fukai Y, Fujii C, Matsuoka M, Iwanami J, Wakabayashi A, Sakuta R. Prevalence of autism spectrum disorder and autistic traits in children with anorexia nervosa and avoidant/restrictive food intake disorder. BioPsychoSocial medicine. 2021; 15(1): 9.

BACKGROUND: Autism spectrum disorder (ASD) and feeding and eating disorders (FEDs) such as anorexia nervosa (AN) are strongly linked as evidenced by frequent comorbidity and overlapping traits. However, eating and social behaviors are shaped by culture, so it is critical to examine these associations in different populations. Moreover, FEDs are heterogeneous, and there has been no examination of autistic traits in avoidant/restrictive food intake disorder (ARFID). METHODS: Therefore, we investigated the prevalence of ASD and autistic traits among Japanese children with AN (n = 92) or ARFID (n = 32) from a prospective multicenter cohort study using the Autism Spectrum Quotient Children’s version (AQC) and Children’s Eating Attitudes Test (ChEAT26). RESULTS: ASD prevalence was high in both AN and ARFID (16.3 and 12.5%, respectively). The AN group exhibited significantly higher scores on all AQC subscales than an age-matched healthy control (HC) group, but there were no significant correlations between AQC scores and ChEAT26 scores. In the AFRID group, AQC scores did not differ from HCs, but significant correlations were found between total AQC and ChEAT26 scores and between several AQC and ChEAT26 subscales. CONCLUSIONS: Both the AN and ARFID groups had high prevalence rates of ASD. The AN group showed a significantly higher degree of autistic traits than the HC group; however, no difference was found between the ARFID and HC groups. Clinicians need to be aware of these rates when working with children with ED.

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10. Joga-Elvira L, Jacas C, Joga ML, Roche-Martínez A, Brun-Gasca C. Pilot study of socio-emotional factors and adaptive behavior in young females with fragile X syndrome. Child neuropsychology : a journal on normal and abnormal development in childhood and adolescence. 2021; 27(7): 949-59.

Girls with Fragile-X-Syndrome (FXS) present high levels of social anxiety, social avoidance, extreme shyness, tendency to social isolation, poor eye contact, learning difficulties, and depression. The aims of the present study, which is based on a group of young females with FXS are: 1) to analyze the possible associations between emotion recognition, theory of mind, and social anxiety, and adaptive behavior, and emotional state; 2) to study the relationship between intelligence quotient (IQ) and adaptive behavior; and 3) to assess whether social anxiety is more prevalent in girls with FXS. The study has 40 female participants aged between 7 and 16 years (26 positive full mutation FXS and 14 as a control group). A neuropsychological assessment was conducted using the following tests: WISC-V, NEPSY-II, SENA, ADHD Rating Scale, BAS, and ABAS-II. In comparison with the control group, the group with FXS presented a greater association between IQ and self-direction ability, and between emotion recognition and leadership. The FXS group presented higher levels of social anxiety and shyness. In the group of girls with FXS, IQ may have prognostic value for both self-direction ability and social adaptation level.

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11. Oakley B, Tillmann J, Ruigrok A, Baranger A, Takow C, Charman T, Jones E, Cusack J, Doherty M, Violland P, Wroczyńska A, Simonoff E, Buitelaar JK, Gallagher L, Murphy DGM. COVID-19 health and social care access for autistic people: European policy review. BMJ open. 2021; 11(6): e045341.

BACKGROUND: The global COVID-19 pandemic has had an unprecedented impact on European health and social care systems, with demands on testing, hospital and intensive care capacity exceeding available resources in many regions. This has led to concerns that some vulnerable groups, including autistic people, may be excluded from services. METHODS: We reviewed policies from 15 European member states, published in March-July 2020, pertaining to (1) access to COVID-19 tests; (2) provisions for treatment, hospitalisation and intensive care units (ICUs); and (3) changes to standard health and social care. In parallel, we analysed survey data on the lived experiences of 1301 autistic people and caregivers. RESULTS: Autistic people experienced significant barriers when accessing COVID-19 services. First, despite being at elevated risk of severe illness due to co-occurring health conditions, there was a lack of accessibility of COVID-19 testing. Second, many COVID-19 outpatient and inpatient treatment services were reported to be inaccessible, predominantly resulting from individual differences in communication needs. Third, ICU triage protocols in many European countries (directly or indirectly) resulted in discriminatory exclusion from lifesaving treatments. Finally, interruptions to standard health and social care left over 70% of autistic people without everyday support. CONCLUSIONS: The COVID-19 pandemic has further exacerbated existing healthcare inequalities for autistic people, probably contributing to disproportionate increases in morbidity and mortality, mental health and behavioural difficulties, and reduced quality of life. An urgent need exists for policies and guidelines on accessibility of COVID-19 services to be updated to prevent the widespread exclusion of autistic people from services, which represents a violation of international human rights law.

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12. Pugsley K, Scherer SW, Bellgrove MA, Hawi Z. Environmental exposures associated with elevated risk for autism spectrum disorder may augment the burden of deleterious de novo mutations among probands. Molecular psychiatry. 2022; 27(1): 710-30.

Although the full aetiology of autism spectrum disorder (ASD) is unknown, familial and twin studies demonstrate high heritability of 60-90%, indicating a predominant role of genetics in the development of the disorder. The genetic architecture of ASD consists of a complex array of rare and common variants of all classes of genetic variation usually acting additively to augment individual risk. The relative contribution of heredity in ASD persists despite selective pressures against the classic autistic phenotype; a phenomenon thought to be explained, in part, by the incidence of spontaneous (or de novo) mutations. Notably, environmental exposures attributed as salient risk factors for ASD may play a causal role in the emergence of deleterious de novo variations, with several ASD-associated agents having significant mutagenic potential. To explore this hypothesis, this review article assesses published epidemiological data with evidence derived from assays of mutagenicity, both in vivo and in vitro, to determine the likely role such agents may play in augmenting the genetic liability in ASD. Broadly, these exposures were observed to elicit genomic alterations through one or a combination of: (1) direct interaction with genetic material; (2) impaired DNA repair; or (3) oxidative DNA damage. However, the direct contribution of these factors to the ASD phenotype cannot be determined without further analysis. The development of comprehensive prospective birth cohorts in combination with genome sequencing is essential to forming a causal, mechanistic account of de novo mutations in ASD that links exposure, genotypic alterations, and phenotypic consequences.

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13. Scott KE, Schulz SE, Moehrle D, Allman BL, Oram Cardy JE, Stevenson RA, Schmid S. Closing the species gap: Translational approaches to studying sensory processing differences relevant for autism spectrum disorder. Autism research : official journal of the International Society for Autism Research. 2021; 14(7): 1322-31.

The study of sensory phenotypes has great potential for increasing research translation between species, a necessity to decipher the neural mechanisms that contribute to higher-order differences in neurological conditions such as autism spectrum disorder (ASD). Over the past decade, despite separate advances in our understanding of the structural and functional differences within the brain of autistic and non-autistic individuals and in rodent models for ASD, researchers have had difficulty translating the findings in murine species to humans, mostly due to incompatibility in experimental methodologies used to screen for ASD phenotypes. Focusing on sensory phenotypes offers an avenue to close the species gap because sensory pathways are highly conserved across species and are affected by the same risk-factors as the higher-order brain areas mostly responsible for the diagnostic criteria for ASD. By first reviewing how sensory processing has been studied to date, we direct our focus to electrophysiological and behavioral techniques that can be used to study sensory phenotypes consistently across species. Using auditory sensory phenotypes as a template, we seek to improve the accessibility of translational methods by providing a framework for collecting cohesive data in both rodents and humans. Specifically, evoked-potentials, acoustic startle paradigms, and psychophysical detection/discrimination paradigms can be created and implemented in a coordinated and systematic fashion across species. Through careful protocol design and collaboration, sensory processing phenotypes can be harnessed to bridge the gap that exists between preclinical animal studies and human testing, so that mutually held questions in autism research can be answered. LAY SUMMARY: It has always been difficult to relate results from animal research to humans. We try to close this gap by studying changes in sensory processing using careful protocol design and collaboration between clinicians and researchers. Sensory pathways are comparable between animals and humans, and are affected in the same way as the rest of the brain in ASD. Using changes in hearing as a template, we point the field in an innovative direction by providing a framework for collecting cohesive data in rodents and humans.

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14. Taylor LJ, Eggleston MJ, Thabrew H, van der Meer L, Waddington H, Whitehouse AJ, Evans K. An investigation of adherence to best practice guidelines for autism diagnosis in New Zealand. Autism : the international journal of research and practice. 2021; 25(7): 2087-100.

Many clinicians in New Zealand do not follow guidelines for best practice in autism diagnosis. In this study, we investigated the processes that health professionals in New Zealand follow when diagnosing autistic children and adults. We asked 117 health professionals from a range of services and regions in New Zealand, how they identify and diagnose autism. We found that there are differences in the way that clinicians in New Zealand diagnose autism. We identified areas in which autism diagnosis in New Zealand could be improved, for example, by establishing more services to diagnose autism in adolescents and adults, and providing more consistent support after a person is diagnosed with autism. These findings will help to improve autism diagnosis in New Zealand.

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15. Vermudez SAD, Gogliotti RG, Arthur B, Buch A, Morales C, Moxley Y, Rajpal H, Conn PJ, Niswender CM. Profiling beneficial and potential adverse effects of MeCP2 overexpression in a hypomorphic Rett syndrome mouse model. Genes, brain, and behavior. 2022; 21(1): e12752.

De novo loss-of-function mutations in methyl-CpG-binding protein 2 (MeCP2) lead to the neurodevelopmental disorder Rett syndrome (RTT). Despite promising results from strategies aimed at increasing MeCP2 levels, additional studies exploring how hypomorphic MeCP2 mutations impact the therapeutic window are needed. Here, we investigated the consequences of genetically introducing a wild-type MECP2 transgene in the Mecp2 R133C mouse model of RTT. The MECP2 transgene reversed the majority of RTT-like phenotypes exhibited by male and female Mecp2 R133C mice. However, three core symptom domains were adversely affected in female Mecp2(R133C/+) animals; these phenotypes resemble those observed in disease contexts of excess MeCP2. Parallel control experiments in Mecp2(Null/+) mice linked these adverse effects to the hypomorphic R133C mutation. Collectively, these data provide evidence regarding the safety and efficacy of genetically overexpressing functional MeCP2 in Mecp2 R133C mice and suggest that personalized approaches may warrant consideration for the clinical assessment of MeCP2-targeted therapies.

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