1. Aksu Uzunhan T, Ayaz A. Homozygous exonic and intragenic NRXN1 deletion presenting as either West syndrome or autism spectrum disorder in two siblings. Clinical neurology and neurosurgery. 2022; 214: 107141.

Neurexins (NRXNs) are cell-adhesion molecules that play critical roles in establishing and maintaining synaptic connections. Humans have three NRXN genes (NRXN1, NRXN2, NRXN3) and heterozygous intragenic microdeletions involving NRXN1 have been associated with autism spectrum disorder, attention deficit hyperactivity disorder, intellectual disability, seizures, schizophrenia, and bipolar disorder. Bi-allelic loss in NRXN1 produces a recessive and severe phenotype. We would like to describe the clinical, electroencephalographic, and genetic findings of two siblings, one with a neurodevelopmental disorder with infantile spasms and the other with autism spectrum disorder, having homozygous exonic NRXN1 deletion. A suspicious variant was not detected in the whole exome-sequencing but copy number variation analysis revealed NRXN1 exon 2-5 homozygous deletion (chr2:51149007-51255411; 106.404 kb) in both siblings. Neurodevelopmental disorder with infantile spasms and autism spectrum disorder in two siblings with homozygous NRXN1 deletion display intrafamilial phenotypic variation. Bi-allelic/homozygous NRXN1 exonic deletions are responsible for a spectrum from significant intellectual disability to epileptic encephalopathy, even within the same family. Array comparative genomic hybridization should be the first genetic testing in epileptic encephalopathy although we reached the diagnosis with next-generation sequencing and later copy number variation analysis.

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2. Alenezi S, Alyahya A, Aldhalaan H. Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) With Language Impairment Accompanied by Developmental Disability Caused by Forkhead Box Protein 1 (FOXP1) Exon Deletion: A Case Report. Cureus. 2021; 13(12): e20595.

Forkhead box protein 1 (FOXP1) (OMIM: 605515) is located at chromosomal region 3p14.1, which codes for a transcriptional repressor protein. FOXP1 syndrome (FOXP1S) (OMIM #613670) is caused by FOXP1 gene deletions and mutations (nonsense, missense, and in-frame deletions). It is identified by the presence of intellectual disability with language impairment, with or without autistic features. This paper describes the case of a seven-year-old girl mainly presenting with autism spectrum disorder, language impairment, and intellectual disability. In addition, she also exhibited signs of attention deficit hyperactivity disorder. Whole-exome sequencing showed that she had a mutation in the FOXP1 gene; the variant revealed was FOXP1: NM_001244813 with a deleted segment (1152-1164) of exon 11. Subsequently, she was diagnosed with FOXP1 syndrome. In order to manage behavioral disturbance, risperidone was given, and she showed marked improvement. In this article, we report the characteristic features of attention deficits hyperactivity in addition to previously reported autism spectrum disorder with language impairment accompanied by intellectual disability caused by FOXP1 exon deletion. This study aims to provide a systematic, comprehensive presentation of a patient with a FOXP1 mutation to contribute to the existing literature on this subject.

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3. Baird A, Papachristou E, Hassiotis A, Flouri E. The role of physical environmental characteristics and intellectual disability in conduct problem trajectories across childhood: A population-based Cohort study. Environmental research. 2022; 209: 112837.

BACKGROUND: The paucity of research investigating the role of the physical environment in the developmental progression of conduct problems and the potential moderating effects of intellectual disability (ID) is surprising, given the clinical relevance of elucidating environmental determinants of disruptive behaviours. AIMS: To use data from a large UK cohort study to assess associations between physical environmental exposures, ID, and conduct problem trajectories. METHOD: The sample included 8168 Millennium Cohort Study children (1.9% with ID). Multilevel growth curve modelling was used to examine the role of physical environment characteristics in the developmental trajectories of conduct problems after adjustments for ID status. RESULTS: Exposure to external environmental domains was not associated with differences in children’s conduct problems across development. Alternatively, internal aspects of the household environment: spatial density (b = 0.40, p < .001) and damp problems (b = 0.14, p < .001) were both significantly associated with increased trajectories. Various individual and familial covariates were positively associated with conduct problems over time, including: presence of ID (b = 0.96, p < .001), autism spectrum disorder (b = 1.18, p < .001), male sex (b = 0.26, p < .001), poverty (b = 0.19, p < .001), maternal depression (b = 0.65, p < .001), and non-nuclear family structure (b = 0.35, p < .001). Positive ID status appeared to moderate the effects of internal household spatial density, reporting a non-linear negative association with spatial density and conduct problems across development (b = -1.08, p < .01). CONCLUSIONS: Our findings highlight the potential harmful consequences of poor internal residential conditions on children's development of disruptive behaviours.

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4. Bodnar TS, Lee C, Wong A, Rubin I, Wegener Parfrey L, Weinberg J. Evidence for long-lasting alterations in the fecal microbiota following prenatal alcohol exposure. Alcoholism, clinical and experimental research. 2022; 46(4): 542-55.

BACKGROUND: There is growing evidence that the gut microbiota can be shaped by early-life experiences/exposures, with long-term consequences for brain, behavior, and health. Changes in the gut microbiota have also been identified in neurodevelopmental disorders including Autism Spectrum Disorder and schizophrenia. In contrast, no studies to date have investigated whether the gut microbiota is altered in individuals with Fetal Alcohol Spectrum Disorder (FASD), the neurodevelopmental disorder that results from prenatal alcohol exposure (PAE). The current study was designed to assess the impact of PAE on the fecal microbiota. METHODS: We used a rodent model in which pregnant Sprague-Dawley rats were provided with an EtOH-containing diet or a control diet throughout gestation. Fecal samples were collected from adult male and female animals and 16s rRNA sequencing was performed. RESULTS: Overall, PAE rats showed greater richness of bacterial species, with community structure investigations demonstrating distinct clustering by prenatal treatment. In addition, prenatal treatment and sex-specific alterations were observed for many specific microbes. For example, in males, Bacteroides and Bifidobacterium, and in females, Faecalitalea and Proteus, differed in abundance between PAE and control rats. CONCLUSIONS: Taken together, these results show for the first time that PAE has a long-lasting and sex-specific impact on the fecal microbiota. Further research is needed that considers fetal microbiota in the development of new interventions in FASD.

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5. Brown HK, Saha S, Chan TCY, Cheung AM, Fralick M, Ghassemi M, Herridge M, Kwan J, Rawal S, Rosella L, Tang T, Weinerman A, Lunsky Y, Razak F, Verma AA. Outcomes in patients with and without disability admitted to hospital with COVID-19: a retrospective cohort study. CMAJ : Canadian Medical Association journal = journal de l’Association medicale canadienne. 2022; 194(4): E112-e21.

BACKGROUND: Disability-related considerations have largely been absent from the COVID-19 response, despite evidence that people with disabilities are at elevated risk for acquiring COVID-19. We evaluated clinical outcomes in patients who were admitted to hospital with COVID-19 with a disability compared with patients without a disability. METHODS: We conducted a retrospective cohort study that included adults with COVID-19 who were admitted to hospital and discharged between Jan. 1, 2020, and Nov. 30, 2020, at 7 hospitals in Ontario, Canada. We compared in-hospital death, admission to the intensive care unit (ICU), hospital length of stay and unplanned 30-day readmission among patients with and without a physical disability, hearing or vision impairment, traumatic brain injury, or intellectual or developmental disability, overall and stratified by age (≤ 64 and ≥ 65 yr) using multivariable regression, controlling for sex, residence in a long-term care facility and comorbidity. RESULTS: Among 1279 admissions to hospital for COVID-19, 22.3% had a disability. We found that patients with a disability were more likely to die than those without a disability (28.1% v. 17.6%), had longer hospital stays (median 13.9 v. 7.8 d) and more readmissions (17.6% v. 7.9%), but had lower ICU admission rates (22.5% v. 28.3%). After adjustment, there were no statistically significant differences between those with and without disabilities for in-hospital death or admission to ICU. After adjustment, patients with a disability had longer hospital stays (rate ratio 1.36, 95% confidence interval [CI] 1.19-1.56) and greater risk of readmission (relative risk 1.77, 95% CI 1.14-2.75). In age-stratified analyses, we observed longer hospital stays among patients with a disability than in those without, in both younger and older subgroups; readmission risk was driven by younger patients with a disability. INTERPRETATION: Patients with a disability who were admitted to hospital with COVID-19 had longer stays and elevated readmission risk than those without disabilities. Disability-related needs should be addressed to support these patients in hospital and after discharge.

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6. Fieiras C, Chen MH, Escobar Liquitay CM, Meza N, Rojas V, Franco JVA, Madrid E. Risperidone and aripiprazole for autism spectrum disorder in children: an overview of systematic reviews. BMJ evidence-based medicine. 2022.

OBJECTIVES: To assess the effectiveness and safety of risperidone and aripiprazole in children with autism spectrum disorder (ASD). DESIGN AND SETTING: Overview of systematic reviews (SRs). SEARCH METHODS: In October 2021, we searched Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycInfo and Epistemonikos placing no restrictions on language or date of publication. PARTICIPANTS: Children aged 12 years or less with ASD. INTERVENTIONS: Risperidone and aripiprazole with no dosage restrictions. DATA COLLECTION AND ANALYSIS: We rated the methodological quality of the included SRs using A Measurement Tool to Assess Systematic Reviews (AMSTAR 2). We reported the Grading of Recommendations, Assessment, Development and Evaluation certainty of the evidence according to the analysis conducted by the authors of the included SRs. MAIN OUTCOMES MEASURED: A multidisciplinary group of experts agreed on analysing nine critical outcomes evolving core and non-core ASD symptoms. PATIENT AND PUBLIC INVOLVEMENT: Organisations of parents of children with ASD were involved during part of the process, participating in external revision of the final version of the report for the Chilean Ministry of Health with no additional comments (ID 757-22-L120 DIPRECE, Ministry of Health, Chile). The organisations involved were: Fundación Unión Autismo y Neurodiversidad, Federación Nacional de Autismo, Vocería Autismo del Sur, and Vocería Autismo del Norte. RESULTS: We identified 22 SRs within the scope of this overview, of which 16 were of critically low confidence according to AMSTAR 2 and were excluded from the analysis. Both aripiprazole and risperidone were effective for reducing autism symptoms severity, repetitive behaviours, inappropriate language, social withdrawal and behavioural problems compared with placebo. The certainty of the evidence for most outcomes was moderate. Risperidone and aripiprazole are associated with metabolic and neurological adverse events. Follow-up was short termed. CONCLUSIONS: We found that aripiprazole and risperidone probably reduce symptom severity at short-term follow-up but may also cause adverse events. High-quality and updated SRs and larger randomised controlled trials with longer term follow-up are needed on this topic. OVERVIEW PROTOCOL: PROSPERO CRD42020206535.

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7. Getz SA, Tariq K, Marchand DH, Dickson CR, Howe Vi JR, Skelton PD, Wang W, Li M, Barry JM, Hong J, Luikart BW. PTEN Regulates Dendritic Arborization by Decreasing Microtubule Polymerization Rate. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2022; 42(10): 1945-57.

Phosphatase and tensin homolog (PTEN) is a major negative regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway. Loss-of-function mutations in PTEN have been found in a subset of patients with macrocephaly and autism spectrum disorder (ASD). PTEN loss in neurons leads to somal hypertrophy, aberrant migration, dendritic overgrowth, increased spine density, and hyperactivity of neuronal circuits. These neuronal overgrowth phenotypes are present on Pten knock-out (KO) and reconstitution with autism-associated point mutations. The mechanism underlying dendritic overgrowth in Pten deficient neurons is unclear. In this study, we examined how Pten loss impacts microtubule (MT) dynamics in both sexes using retroviral infection and transfection strategies to manipulate PTEN expression and tag the plus-end MT binding protein, end-binding protein 3 (EB3). We found Pten KO neurons sprout more new processes over time compared with wild-type (WT) neurons. We also found an increase in MT polymerization rate in Pten KO dendritic growth cones. Reducing MT polymerization rate to the WT level was sufficient to reduce dendritic overgrowth in Pten KO neurons in vitro and in vivo Finally, we found that rescue of dendritic overgrowth via inhibition of MT polymerization was sufficient to improve the performance of Pten KO mice in a spatial memory task. Taken together, our data suggests that one factor underlying PTEN loss dependent dendritic overgrowth is increased MT polymerization. This opens the possibility for an intersectional approach targeting MT polymerization and mTOR with low doses of inhibitors to achieve therapeutic gains with minimal side effects in pathologies associated with loss of neuronal PTEN function.SIGNIFICANCE STATEMENT Loss of Pten function because of genetic deletion or expression of mutations associated with autism spectrum disorder (ASD), results in overgrowth of neurons including increased total dendritic length and branching. We have discovered that this overgrowth is accompanied by increased rate of microtubule (MT) polymerization. The increased polymerization rate is insensitive to acute inhibition of mechanistic target of rapamycin (mTOR)C1 or protein synthesis. Direct pharmacological inhibition of MT polymerization can slow the polymerization rate in Pten knock-out (KO) neurons to rates seen in wild-type (WT) neurons. Correction of the MT polymerization rate rescues increased total dendritic arborization and spatial memory. Our studies suggest that phosphatase and tensin homolog (PTEN) inhibits dendritic growth through parallel regulation of protein synthesis and cytoskeletal polymerization.

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8. Key AP, Jones D, Corbett BA. Sex differences in automatic emotion regulation in adolescents with autism spectrum disorder. Autism research : official journal of the International Society for Autism Research. 2022; 15(4): 712-28.

Autism may be underdiagnosed in females because their social difficulties are often less noticeable. This study explored sex differences in automatic facial emotion processing in 45 adolescents with autism spectrum disorder (22 female, 23 male), age 10-16 years, performing active target detection task and Go/NoGo tasks where faces with positive and negative emotional expressions served as irrelevant distractors. The combined sample demonstrated more accurate performance on the target detection (response initiation) than the Go/NoGo task (response inhibition), replicating findings previously reported in typical participants. Females exhibited greater difficulty than males with response initiation in the target detection task, especially in the context of angry faces, while males found withholding a response in the Go/NoGo block with happy faces more challenging. Electrophysiological data revealed no sex differences or emotion discrimination effects during the early perceptual processing of faces indexed by the occipitotemporal N170. Autistic males demonstrated increased frontal N2 and parietal P3 amplitudes compared to females, suggesting greater neural resource allocation to automatic emotion regulation processes. The associations between standardized behavioral measures (autism severity, theory of mind skills) and brain responses also varied by sex: more adaptive social functioning was related to the speed of perceptual processing (N170 latency) in females and the extent of deliberate attention allocation (P3 amplitudes) in males. Together, these findings suggest that males and females with autism may rely on different strategies for social functioning and highlight the importance of considering sex differences in autism. LAY SUMMARY: Females with autism may exhibit less noticeable social difficulties than males. This study demonstrates that autistic females are more successful than males at inhibiting behavioral responses in emotional contexts, while males are more likely to initiate a response. At the neural level, social functioning in females is related to the speed of automatic perceptual processing of facial cues, and in males, to the extent of active attention allocation to the stimuli. These findings highlight the importance of considering sex differences in autism diagnosis and treatment selection.

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9. Kryszak EM, Albright CM, Fell LA, Butter EM, Kuhlthau KA. Clinician Perspectives on Telehealth Assessment of Autism Spectrum Disorder During the COVID-19 Pandemic. Journal of autism and developmental disorders. 2022: 1-16.

This study examined clinician insights into telehealth assessment services for autism spectrum disorder implemented during the COVID-19 pandemic. 35 clinicians from multiple disciplines across 17 sites in the Autism Care Network were interviewed. Themes identified through qualitative analyses included factors related to confidence in diagnosis (impressions of in-home observation; child and family factors that affected diagnostic confidence; changes in rapport); patient and family factors related to telehealth (perceived family benefits of and barriers to telehealth; factors related to healthcare disparities; factors specific to non-native English speakers); and institutional and workplace factors related to transitioning to telehealth (institutional support; changes to efficacy, attendance, and work satisfaction). Results suggest that telehealth has potential to be an effective tool in autism assessment practice.

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10. Montobbio N, Cavallo A, Albergo D, Ansuini C, Battaglia F, Podda J, Nobili L, Panzeri S, Becchio C. Intersecting kinematic encoding and readout of intention in autism. Proceedings of the National Academy of Sciences of the United States of America. 2022; 119(5).

Observers with autism spectrum disorders (ASDs) find it difficult to read intentions from movements. However, the computational bases of these difficulties are unknown. Do these difficulties reflect an intention readout deficit, or are they more likely rooted in kinematic (dis-)similarities between typical and ASD kinematics? We combined motion tracking, psychophysics, and computational analyses to uncover single-trial intention readout computations in typically developing (TD) children (n = 35) and children with ASD (n = 35) who observed actions performed by TD children and children with ASD. Average intention discrimination performance was above chance for TD observers but not for ASD observers. However, single-trial analysis showed that both TD and ASD observers read single-trial variations in movement kinematics. TD readers were better able to identify intention-informative kinematic features during observation of TD actions; conversely, ASD readers were better able to identify intention-informative features during observation of ASD actions. Crucially, while TD observers were generally able to extract the intention information encoded in movement kinematics, those with autism were unable to do so. These results extend existing conceptions of mind reading in ASD by suggesting that intention reading difficulties reflect both an interaction failure, rooted in kinematic dissimilarity between TD and ASD kinematics (at the level of feature identification), and an individual readout deficit (at the level of information extraction), accompanied by an overall reduced sensitivity of intention readout to single-trial variations in movement kinematics.

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11. Ozdemir NK, Koç M. Career adaptability of parents of children with autism spectrum disorder. Current psychology (New Brunswick, NJ). 2022: 1-14.

This descriptive phenomenological study examines career adaptability of parents of children with Autism Spectrum Disorder (ASD). Participants include 30 parents (18 fathers and 12 mothers; 6 of them were couples) ranging in age from 26 to 45 years, selected by a purposive sampling method. The semi-structured interview form developed by the researchers based on the Career Construction Theory was used to collect data after receiving expert verification on the questions. In addition, to triangulate data sources, the Participant Feedback Form filled by the participants on the day following the interview and the Researcher Diary filled by the interviewer during the data collection process were utilized. Colaizzi’s seven-step method was followed to analyze the data. Four major domains emerged, highlighting traumas/changes in work-life after ASD, career adaptability, influences of COVID-19 pandemic, and post-interview awareness of this particular sample. Results from the study highlighted looking ahead, being persistent, career decision-making, career-exploration accompanied by some expectations such as more time, income and flexibility, and coping skills build upon the ASD, along with postponement and abandonment of previous career goals, alteration of future career plans, and lack of self-exploration. The results contributed to the theory by providing evidence for career adaptability of parents of children with individual differences, including career adaptability resources and needs. Findings also implied the need for interventions to foster career adaptability skills of parents regarding looking ahead in a positive way, decision-making, self-exploration, and coping with career barriers and difficulties.

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12. Peristeri E, Silleresi S, Tsimpli IM. Bilingualism effects on cognition in autistic children are not all-or-nothing: The role of socioeconomic status in intellectual skills in bilingual autistic children. Autism : the international journal of research and practice. 2022: 13623613221075097.

Previous research has suggested that bilingualism may improve cognition in children with autism, and that this boost may stem from improvement in executive functions. The Wechsler Intelligence Scales for Children are considered to be reliable and valid measures of intelligence when administered to autistic children. These measures have so far revealed unusual psychometric properties in monolingual autistic children, notably distinctive patterns of strengths and weaknesses and low inter-correlation among verbal and nonverbal IQ subtests. The way bilingualism affects the intellectual functioning of autistic children has not been explored yet. Nor has there been a satisfactory factor structure that explains monolingual and bilingual autistic children’s IQ performance in terms of individual factors, such as age and socioeconomic status. The current study examined the intelligence profiles of 316 bilingual and age- and gender-matched monolingual children with autism using the Wechsler Intelligence Scales for Children-Third Edition. The study applied clustering models to extract intelligence subtypes of autism, and mediation analyses to examine potential mediation effects of age and socioeconomic status on the children’s verbal and nonverbal IQ performance. The results support the mediational role of the children’s socioeconomic status in the association between bilingualism and intelligence. Low-socioeconomic status bilingual autistic children outperformed their monolingual peers on both verbal and nonverbal subtests, while the differences faded in medium-socioeconomic status and high-socioeconomic status children. The findings emphasize the positive effects of bilingualism on low-socioeconomic status autistic children’s intelligence and also highlight high-socioeconomic status as a factor that may mitigate discrepant patterns of strengths and weaknesses in monolingual children’s IQ performance.

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13. Smith JR, Pierce DL. Letter to the Editor: Aripiprazole-Induced Hypersexuality in an Autistic Child. Journal of child and adolescent psychopharmacology. 2022; 32(1): 70-1.

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14. Wang H, Ma ZH, Xu LZ, Yang L, Ji ZZ, Tang XZ, Liu JR, Li X, Cao QJ, Liu J. Developmental brain structural atypicalities in autism: a voxel-based morphometry analysis. Child and adolescent psychiatry and mental health. 2022; 16(1): 7.

BACKGROUND: Structural magnetic resonance imaging (sMRI) studies have shown atypicalities in structural brain changes in individuals with autism spectrum disorder (ASD), while a noticeable discrepancy in their results indicates the necessity of conducting further researches. METHODS: The current study investigated the atypical structural brain features of autistic individuals who aged 6-30 years old. A total of 52 autistic individuals and 50 age-, gender-, and intelligence quotient (IQ)-matched typically developing (TD) individuals were included in this study, and were assigned into three based cohorts: childhood (6-12 years old), adolescence (13-18 years old), and adulthood (19-30 years old). Analyses of whole-brain volume and voxel-based morphometry (VBM) on the sMRI data were conducted. RESULTS: No significant difference was found in the volumes of whole-brain, gray matter, and white matter between the autism and TD groups in the three age-based cohorts. For VBM analyses, the volumes of gray matter in the right superior temporal gyrus and right inferior parietal lobule in the autism group (6-12 years old) were smaller than those in the TD group; the gray matter volume in the left inferior parietal lobule in the autism group (13-18 years old) was larger than that in the TD group; the gray matter volume in the right middle occipital gyrus in the autism group (19-30 years old) was larger than that in the TD group, and the gray matter volume in the left posterior cingulate gyrus in the autism group was smaller than that in the TD group. CONCLUSION: Autistic individuals showed different atypical regional gray matter volumetric changes in childhood, adolescence, and adulthood compared to their TD peers, indicating that it is essential to consider developmental stages of the brain when exploring brain structural atypicalities in autism.

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15. Xu T, Qian X, Rifenbark GG, Shogren KA, Hagiwara M. Psychometric Properties of Self-Determination Inventory: Student Report Among Chinese Students With and Without Intellectual and Developmental Disabilities. Intellectual and developmental disabilities. 2022; 60(1): 41-56.

This study explores the psychometric properties of Self-Determination Inventory: Student Report (SDI:SR) in students with intellectual and developmental disabilities (IDD) and without disabilities in China. The paper-and-pencil version of SDI:SR Chinese Translation (SDI:SR Chinese) was used to explore self-determination across students with IDD (n = 245) and students without disabilities (n = 315) from 16 schools across six cities in China. We examined the factor structure of the measure, conducted analysis of measurement invariance, and compared the latent means across students with IDD and without disabilities. Findings suggest that the data fit a one-factor model better than a three-factor model. We found greater variability in self-determination among students with IDD than students without disabilities. However, the two groups did not differ in latent means.

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16. Zhou X, Shi W, Ye M, Chen S, Xu N, Xu C. High normal sized CGG repeat on the FMR1 gene reduces live birth rates after in vitro fertilization in Han Chinese. Gene. 2022; 819: 146204.

Substantial evidence now suggests an association between the FMR1 genotype and female fertility. The aim of this study was to determine whether a high normal FMR1 allele (35-54 repeats) affects in vitro fertilization (IVF) outcomes in Chinese women. A total of 120 women with 210 IVF cycles were retrospectively recruited in this study. The patients were divided into two groups based on the FMR1 repeat lengths at allele 2 (normal repeat group: <35 repeats; high repeat group: 35-54 repeats). The observed primary outcomes were the clinical pregnancy rate and live birth rate. No associations were observed between the high normal FMR1 allele and lower clinical pregnancy rate or live birth rate after adjusting for maternal age, education, work status, duration of infertility and number of embryos transferred (aOR 0.633, 95% CI 0.249-1.601, p = 0.337; aOR 0.325, 95% CI 0.094-1.118, p = 0.075; respectively). However, after additionally adjusting for anti-Müllerian hormone (AMH) level, there was a weak but significant association between high normal sized CGG repeats and a lower live birth rate (aOR 0.218, 95% CI 0.057-0.836, p = 0.026). The rate of available embryos showed a decreasing trend in patients with a high normal FMR1 allele, although the difference was not statistically significant after adjusting for maternal age, education, work status, duration of infertility and AMH level (aOR 0.905, 95% CI 0.810-1.011, p = 0.078). Furthermore, the number of CGG repeats in either allele was not associated with the live birth rate after adjusting for all confounding factors (aOR 0.832, 95% CI 0.677-1.023, p = 0.081; aOR 0.865, 95% CI 0.651-1.148, p = 0.315; respectively). In addition, no significant differences were found in the rates of good-quality embryos (p = 0.263), miscarriage (p = 0.861) or cycle cancellation (p = 0.295) between the groups. Taken together, in the Chinese population, individuals with high normal sized CGG repeats on the FMR1 gene have a higher risk of reduced live birth rates in childbearing age. Therefore, we recommend enhanced screening for fragile X syndrome in women of childbearing age in China. This study also suggests that the association between the FMR1 genotype and fertility in Chinese women merits further research.

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