1. Lu L, Guo H, Peng Y, Xun G, Liu Y, Xiong Z, Tian D, Li W, Xu X, Zhao J, Hu Z, Xia K. {{Common and rare variants of the THBS1 gene associated with the risk for autism}}. {Psychiatr Genet};2014 (Oct 10)
OBJECTIVES: Autism is a severe neurodevelopmental disorder. Many susceptible or causative genes have been identified, and most of them are related to synaptogenesis. The THBS1 gene encodes thrombospondin 1, which plays a critical role in synaptogenesis of the central nervous system in the developing brain. However, no study has been carried out revealing that THBS1 is an autism risk gene. METHODS: We analyzed the whole coding region and the 5′-untranslated region of the THBS1 gene in 313 autistic patients by Sanger sequencing, which was also used to analyze the identified variants in 350 normal controls. Association analysis was carried out using PLINK or R. Haplotype analysis was carried out using Haploview. Functional prediction and conservation analysis of missense variants were carried out using ANNOVAR. RESULTS: Twelve variants, including five common variants and seven rare variants, were identified in the THBS1 coding region and the 5′-untranslated region. Among them, one common variant (c.1567A>G:p.T523A) was significantly associated with autism (P<0.05). Two rare variants (c.2429G>A:p.R810Q, c.3496G>C:p.E1166Q) were absent in the 350 controls and were not reported in the single nucleotide polymorphism database (dbSNP). Combined association analysis of the rare variants (minor allele frequency<0.01) in patients and Asian samples in the 1000 genome project revealed a significant association between these rare variants and autism (P=0.039). CONCLUSION: Our data revealed that both common and rare variants of the THBS1 gene are associated with risk for autism, suggesting that THBS1 is a novel susceptible gene for autism.
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2. Winkler-Schwartz A, Garfinkle J, Shevell MI. {{Autism Spectrum Disorder in a Term Birth Neonatal Intensive Care Unit Population}}. {Pediatr Neurol};2014 (Jul 16)
BACKGROUND: Nonspecific perinatal risk factors have been revealed to be associated with the development of autism spectrum disorder. However, term at-risk infants, as a distinct population, are underrepresented in the literature. This study examines the incidence and neonatal risk factors for autism spectrum disorder in term neonatal intensive care unit survivors. METHODS: We performed a retrospective analysis from a single university-practice database of neonates admitted to the neonatal intensive care unit and followed by a single pediatric neurologist. Term infants (>/=37 weeks), born between 1991 and 2011, with at least 2 years (or 1 year if found to be neurologically normal) of follow-up were included. Principle outcomes were autism spectrum disorder, cerebral palsy, global developmental delay, and epilepsy. RESULTS: One hundred eighty infants were included from a database of 564 neonates. Twelve (6.6%) developed autism spectrum disorder, 53 (29.4%) cerebral palsy, 77 (42.7%) global developmental delay, and 47 (26.1%) epilepsy. Seventy-one (39.4%) developed no adverse outcomes. Nine patients with autism spectrum disorder (75%) were diagnosed with at least one other adverse outcome. No neonatal or perinatal variables were evident to be significantly associated with later autism spectrum disorder. CONCLUSIONS: In term neonatal intensive care unit survivors, autism spectrum disorder occurs at a greater frequency than in the general population and often develops alongside comorbid conditions. This highlights the importance of screening term neonatal intensive care unit survivors for autism spectrum disorder, particularly when comorbidities are present.
