1. Ali NH, Khalaf SK, Al-Asadi JN, Abed AH. {{Maternal antineuronal antibodies and risk of childhood autism spectrum disorders: A case-control study}}. {J Chin Med Assoc};2016 (Sep 26)
BACKGROUND: The etiology of autism is complex, and may involve the interaction between genetic and environmental factors. Recent studies suggested an association between maternal immune response and this disorder. METHODS: Forty-nine women with autistic children (cases) were studied in comparison with 73 women with normal children (controls). After interviewing for sociodemographic and clinical information, mothers’ sera were tested for the presence of antineuronal antibodies. RESULTS: Mothers of autistic children had significantly higher seropositivity for anti-Yo antibodies (34.7%) than control women (13.7%), with an (adjusted odds ratio of 2.60 (95% confidence interval, 1.03-6.61; p=0.044). Similarly, women with autistic children showed significantly higher seropositivity for antiamphiphysin than the control group (40.8% vs. 17.8%), with an adjusted odds ratio of 2.54 (95% confidence interval, 1.07-6.04; p=0.035). No significant association was found between autism spectrum disorders and maternal anti-Hu antibodies and anti-Ri antibodies, and the history of autoimmune diseases. CONCLUSION: Some maternal antineuronal antibodies may contribute significantly to the risk of childhood autism.
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2. Caubit X, Gubellini P, Andrieux J, Roubertoux PL, Metwaly M, Jacq B, Fatmi A, Had-Aissouni L, Kwan KY, Salin P, Carlier M, Lieden A, Rudd E, Shinawi M, Vincent-Delorme C, Cuisset JM, Lemaitre MP, Abderrehamane F, Duban B, Lemaitre JF, Woolf AS, Bockenhauer D, Severac D, Dubois E, Zhu Y, Sestan N, Garratt AN, Le Goff LK, Fasano L. {{TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons}}. {Nat Genet};2016 (Sep 26)
TSHZ3, which encodes a zinc-finger transcription factor, was recently positioned as a hub gene in a module of the genes with the highest expression in the developing human neocortex, but its functions remained unknown. Here we identify TSHZ3 as the critical region for a syndrome associated with heterozygous deletions at 19q12-q13.11, which includes autism spectrum disorder (ASD). In Tshz3-null mice, differentially expressed genes include layer-specific markers of cerebral cortical projection neurons (CPNs), and the human orthologs of these genes are strongly associated with ASD. Furthermore, mice heterozygous for Tshz3 show functional changes at synapses established by CPNs and exhibit core ASD-like behavioral abnormalities. These findings highlight essential roles for Tshz3 in CPN development and function, whose alterations can account for ASD in the newly defined TSHZ3 deletion syndrome.
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3. Gigonzac MA, Teodoro LS, Minasi LB, Vieira TC, da Cruz AD. {{Standardization of capillary electrophoresis for diagnosis of fragile x syndrome in the brazilian public health system}}. {Electrophoresis};2016 (Sep 26)
Fragile X Syndrome (FXS) is the most common cause of inherited intellectual disability. The most common etiology of the syndrome is expansion and methylation of a CGG trinucleotide at chromosome region Xq27.3 involving FMR1. This disorder is commonly underdiagnosed in children and adolescents, given the high clinical variability. In Brazil, molecular diagnosis of FXS by capillary electrophoresis does not exist in the public health system. The current standard for separation and identification of DNA fragment sizes is 50 cm capillary electrophoresis, which is uncommon in public genotyping laboratories. This study describes the standardization of 36 cm capillary electrophoresis for fragment analysis of samples from patients with intellectual disability suggestive of FXS. Genomic dsDNA was isolated from patients and amplified by PCR using the FMR1 AmplideX(R) Kit. It was then possible to detect changes in repeat length of FMR1, such as full mutation and pre-mutation. Thus, the proposed standardization proved to be effective for the diagnosis of FXS, permitting suitable genetic counseling for families. Inclusion of molecular testing such as this in the Brazilian public health service bridges the gap between available technologies and effective diagnosis, universalizing access to genetic testing in central Brazil. This article is protected by copyright. All rights reserved.
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4. Healy S, Haegele JA, Grenier M, Garcia JM. {{Physical Activity, Screen-Time Behavior, and Obesity Among 13-Year Olds in Ireland with and without Autism Spectrum Disorder}}. {J Autism Dev Disord};2016 (Sep 26)
The primary purposes of this study were to compare (a) physical activity participation, screen-time habits, obesity, and (b) reported reasons for lack of participation in sport, between a nationally representative sample of Irish children with and without autism spectrum disorder (ASD). Participation in moderate to vigorous activity, light activity, and sports was significantly lower among the group with ASD. On examination of screen time variables, no significant differences were seen between groups. However, time spent watching TV was higher among children with ASD. Overweight or obese status was more prevalent among the group with ASD (34.4 vs. 24.7 %). The findings are discussed in relation to international statistics on youth physical activity, screen-time, and weight status, and recommendations are provided for future research.
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5. Novo-Filho GM, Montenegro MM, Zanardo EA, Dutra RL, Dias AT, Piazzon FB, Costa TV, Nascimento AM, Honjo RS, Kim CA, Kulikowski LD. {{Subtelomeric Copy Number Variations: The Importance of 4p/4q Deletions in Patients with Congenital Anomalies and Developmental Disability}}. {Cytogenet Genome Res};2016 (Sep 24)
The most prevalent structural variations in the human genome are copy number variations (CNVs), which appear predominantly in the subtelomeric regions. Variable sizes of 4p/4q CNVs have been associated with several different psychiatric findings and developmental disability (DD). We analyzed 105 patients with congenital anomalies (CA) and developmental and/or intellectual disabilities (DD/ID) using MLPA subtelomeric specific kits (P036 /P070) and 4 of them using microarrays. We found abnormal subtelomeric CNVs in 15 patients (14.3%), including 8 patients with subtelomeric deletions at 4p/4q (53.3%). Additional genomic changes were observed at 1p36, 2q37.3, 5p15.3, 5q35.3, 8p23.3, 13q11, 14q32.3, 15q11.2, and Xq28/Yq12. This indicates the prevalence of independent deletions at 4p/4q, involving PIGG, TRIML2, and FRG1. Furthermore, we identified 15 genes with changes in copy number that contribute to neurological development and/or function, among them CRMP1, SORCS2, SLC25A4, and HELT. Our results highlight the association of genes with changes in copy number at 4p and 4q subtelomeric regions and the DD phenotype. Cytogenomic characterization of additional cases with distal deletions should help clarifying the role of subtelomeric CNVs in neurological diseases.
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6. Wu YW, Kuzniewicz MW, Croen L, Walsh EM, McCulloch CE, Newman TB. {{Risk of Autism Associated With Hyperbilirubinemia and Phototherapy}}. {Pediatrics};2016 (Sep 26)
OBJECTIVE: Whether neonatal hyperbilirubinemia and/or phototherapy increase the risk of autism spectrum disorder (ASD) is unclear. We sought to quantify the risk of ASD associated with elevated total serum bilirubin (TSB) levels and with phototherapy. METHODS: In a retrospective cohort study of 525 409 infants born at >/=35 weeks’ gestation in 15 Kaiser Permanente Northern California (KPNC) hospitals, 1995-2011, we obtained all TSB levels and determined which infants received phototherapy. From the KPNC Autism Registry, we identified patients with ASD diagnosed at a KPNC Autism Center, by a clinical specialist, or by a pediatrician. We calculated Cox proportional hazard ratios (HRs) for time to diagnosis of ASD, adjusting for confounding factors. RESULTS: Among infants in the birth cohort, 2% had at least 1 TSB level >/=20 mg/dL, and 8% received phototherapy. The rate of ASD was 13 per 1000 births. Crude analyses revealed an association between TSB >/=20 and ASD (relative risk: 1.4; 95% confidence interval [CI]: 1.1-1.6), and between phototherapy and ASD (relative risk: 1.7; 95% CI: 1.5-1.8). After adjusting for confounders, TSB >/=20 (HR: 1.09; 95% CI: 0.89-1.35) and phototherapy (HR: 1.10; 95% CI: 0.98-1.24) were no longer significantly associated with ASD. Independent risk factors for ASD included maternal and paternal age; maternal and paternal higher education; male sex; birth weight <2500 g or >/=4200 g; and later year of birth. CONCLUSIONS: After adjustment for the effects of sociodemographic factors and birth weight, neither hyperbilirubinemia nor phototherapy was an independent risk factor for ASD.
