sj-docx-1-whe-10.1177_17455057221133635 – Supplemental material for Mental health and neurodevelopment in children and adolescents with Turner syndrome

Supplemental material, sj-docx-1-whe-10.1177_17455057221133635 for Mental health and neurodevelopment in children and adolescents with Turner syndrome by Jeanne Wolstencroft, William Mandy and David Skuse in Women’s Health</p

Additional file 3: Table S3. of Social communication and emotion difficulties and second to fourth digit ratio in a large community-based sample

Descriptive statistics of predictors and outcomes stratified by gender

Additional file 1: Table S1. of Social communication and emotion difficulties and second to fourth digit ratio in a large community-based sample

Comparison of sociodemographic data of the ALSPAC cohort and the sample included in the current study

Additional file 2: Table S2. of Social communication and emotion difficulties and second to fourth digit ratio in a large community-based sample

Sociodemographics across sample studied

Additional file 2 of Rare neurodevelopmental conditions and parents’ mental health – how and when does genetic diagnosis matter?

Supplementary Material 1: Supplementary tables and figure

Additional file 2: Table S9. of Shared genetic influences between dimensional ASD and ADHD symptoms during child and adolescent development

Pathway-based dissection of additive genetic variance in SDQ-ADHD and SCDC scores according to 50 molecular signatures database hallmark gene set collections. (XLSX 20 kb

Additional file 1: of Shared genetic influences between dimensional ASD and ADHD symptoms during child and adolescent development

Additional note. Selection of SDQ-ADHD measures. Additional note. Meta-analysis of correlated test statistics from pathway analysis. Additional note. Additional references. Additional note. Web resources. Table S1. Descriptives of SDQ-ADHD and SCDC scores in ALSPAC. Table S2. Phenotypic correlations of SDQ-ADHD scores in ALSPAC. Table S3. Phenotypic correlations of SCDC scores in ALSPAC. Table S4. Univariate GREML of SDQ-ADHD scores in ALSPAC. Table S5. Univariate GREML of SCDC scores in ALSPAC. Table S6. Bivariate GREML of SDQ-ADHD scores in ALSPAC. Table S7. Bivariate GREML of SCDC scores in ALSPAC. Table S8. Bivariate GREML and Pearson correlations of SDQ-ADHD and SCDC scores in ALSPAC. Table S10. Association between ADHD polygenic scores and SDQ-ADHD scores in ALSPAC. Table S11. Association between ASD polygenic scores and SDQ-ADHD scores in ALSPAC. Table S12. Association between ADHD polygenic scores and SCDC scores in ALSPAC. (DOCX 92 kb

DataSheet_1_Utility of the 3Di short version in the identification and diagnosis of autism in children at the Kenyan coast.docx

IntroductionThe precise epidemiological burden of autism is unknown because of the limited capacity to identify and diagnose the disorder in resource-constrained settings, related in part to a lack of appropriate standardised assessment tools and health care experts. We assessed the reliability, validity, and diagnostic accuracy of the Developmental Diagnostic Dimensional Interview (3Di) in a rural setting on the Kenyan coast.MethodsUsing a large community survey of neurodevelopmental disorders (NDDs), we administered the 3Di to 2,110 children aged between 6 years and 9 years who screened positive or negative for any NDD and selected 242 who had specific symptoms suggestive of autism based on parental report and the screening tools for review by a child and adolescent psychiatrist. On the basis of recorded video, a multi-disciplinary team applied the Autism Diagnostic Observation Schedule to establish an autism diagnosis. Internal consistency was used to examine the reliability of the Swahili version of the 3Di, tetrachoric correlations to determine criterion validity, structural equation modelling to evaluate factorial structure and receiver operating characteristic analysis to calculate diagnostic accuracy against Diagnostic Statistical Manual of Mental Disorders (DSM) diagnosis.ResultsThe reliability coefficients for 3Di were excellent for the entire scale {McDonald’s omega (ω) = 0.83 [95% confidence interval (CI) 0.79–0.91]}. A higher-order three-factor DSM-IV-TR model showed an adequate fit with the model, improving greatly after retaining high-loading items and correlated items. A higher-order two-factor DSM-5 model also showed an adequate fit. There were weak to satisfactory criterion validity scores [tetrachoric rho = 0.38 (p = 0.049) and 0.59 (p = 0.014)] and good diagnostic accuracy metrics [area under the curve = 0.75 (95% CI: 0.54–0.96) and 0.61 (95% CI: 0.49–0.73] for 3Di against the DSM criteria. The 3Di had a moderate sensitivity [66.7% (95% CI: 0.22–0.96)] and a good specificity [82.5% (95% CI: 0.74–0.89)], when compared with the DSM-5. However, we observed poor sensitivity [38.9% (95% CI: 0.17–0.64)] and good specificity [83.5% (95% CI: 0.74–0.91)] against DSM-IV-TR.ConclusionThe Swahili version of the 3Di provides information on autism traits, which may be helpful for descriptive research of endophenotypes, for instance. However, for accuracy in newly diagnosed autism, it should be complemented by other tools, e.g., observational clinical judgment using the DSM criteria or assessments such as the Autism Diagnostic Observation Schedule. The construct validity of the Swahili 3Di for some domains, e.g., communication, should be explored in future studies.</p

Genetic alterations identified in the control subject SWE_Q56_508.

<p>A. <i>SHANK2</i> splice mutation (IVS22+1G>T) detected in a Swedish female control, SWE_Q56_508. The mutation altered the donor splicing site of exon 22 and led to a premature stop in all <i>SHANK2</i> isoforms except for the <i>AF1411901</i> isoform, where it altered the protein sequence (G263V). B. CNVs in the same individual altering <i>LOC339822</i>, <i>SNTG2</i>, <i>PXDN</i> and <i>MYT1L</i>. The two close duplications span 264 kb and 245 kb on chromosome 2 and altered <i>LOC339822</i> and <i>SNTG2</i>, and <i>PXDN</i> and <i>MYT1L</i>, respectively. Dots show the B allele frequency (BAF; in green), Log R ratio (LRR; in red), and QuantiSNP score (in blue). Lower panel: all CNVs listed in the Database of Genomic Variants (DGV) are represented: loss (in red), gain (in blue), gain or loss (in brown). H, homer binding site; D, dynamin binding site; C, cortactin binding site.</p

<i>SHANK2</i> mutations in patients with ASD.

<p>A. A heterozygous deletion of <i>SHANK2</i> was identified with the Illumina Human 1M-Duo SNP array in a patient with autism (AU038_3). The deletion spans 421 kb on chromosome 11q13.3, covers twelve exons of the human <i>SHANK2</i> and is not present in the parents. Each dot shows Log R Ratio (LRR; in red) and B allele frequency (BAF; in green). QuantiSNP score is represented with a blue line and indicates the deletion size. B. Location of the CNV and sequence variants (from this study and Berkel <i>et al.</i> 2010) along the SHANK2 protein: in red the variations specific to ASD, in orange the variations shared by ASD and controls and in green the variations specific to controls <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002521#pgen.1002521-Berkel1" target="_blank">[26]</a>. The breakpoints of the <i>SHANK2</i> deletion in AU038_3 are represented with a dotted line on the protein. Stars indicate the variants affecting conserved amino acids. C. A total of 40 variants were identified and variants affecting conserved amino acids in other SHANK proteins are enriched in patients with ASD (n_conserved = 12 and n_{non-conserved} = 3) compared with controls (n_conserved = 6 and n_{non-conserved} = 11) (Fisher's exact test 1-sided, P = 0.013, OR = 6.83, 95% IC = 1.19–53.40). D. The percentage of carriers of <i>SHANK2</i> variants in patients with ASD and Controls. Variants affecting a conserved amino acid among the SHANK proteins are enriched in patients with ASD (n_conserved = 29 and n_{non-conserved} = 822) compared with controls (n_conserved = 16 and n_{non-conserved} = 1074) (Fisher's exact test 1-sided, P = 0.004, OR = 2.37, 95% CI = 1.23–4.70). Open squares and filled squares represent the non-conserved and conserved amino acids, respectively. ANK, Ankyrin repeat domain; SH3, Src homology 3 domain; PDZ, postsynaptic density 95/Discs large/zona occludens-1 homology domain; SAM, sterile alpha motif domain; BSR, brain specific region; H, homer binding site; D, dynamin binding site; C, cortactin binding site. The proline-rich region is represented as a horizontal gray line.</p