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Translational Control Mutations in the fragile X mental retardation 1 ( FMR1 ) gene underlie fragile X syndrome and fragile X–associated primary ovarian insufficiency, which are prominent intellectual disability and reproductive disorders, respectively. FMR1 is thought to reduce protein synthesis (translation) at synapses. In Drosophila oocytes, Greenblatt and Spradling found that Fmr1 loss leads to oocytes that generate embryos exhibiting neural defects (see the Perspective by Aryal and Klann). Ribosome profiling of oocytes identified a specific role for FMR1 in enhancing the translation of large proteins, including many associated with autism. FMR1 seems to help maintain translation of large mRNAs that otherwise condense into inactive ribonucleoprotein particles. This mechanism may underlie other causes of autism and mental dysfunction. Science , this issue p. [709][1]; see also p. [648][2] [1]: /lookup/doi/10.1126/science.aas9963 [2]: /lookup/doi/10.1126/science.aau6450

We know very little about the causes of autism disorders (ASDs), but one effort, led by D. Amaral, has been investigating the effects of exposing pregnant primates to antibodies taken from human mothers of children with ASD. In their latest study, they collected serum from mothers of ASD children that contained antibodies to 37- and 73-kD fetal brain proteins. These two proteins are specifically associated with ASD in humans. Purified immunoglobulin G (IgG), with or without the antibodies, was intravenously delivered to pregnant rhesus macaques. The findings were fascinating: First, mothers exposed to IgG with antibodies were more protective of their young ones. Second, offspring of these mothers more frequently approached their peers (although this behavior did not elicit effective social interaction). Third, magnetic resonance imaging data showed that these offspring had larger brain volumes, particularly in the white matter of the frontal lobe. The alterations in brain volume were observed only in males, whereas behavioral abnormalities were obvious in both genders. How prenatal exposure to maternal antibodies leads to these fetal brain changes is not yet clear. Despite limitations, this article describes a primate model useful for the study of the development of human ASD—one that uses a specific etiology derived from the clinical population. Among other needed experiments, this model will allow investigation into the histological correlates of ASD and looks promising in establishing specific targets for therapeutic interventions. M. D. Bauman et al. , Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey. Transl. Psych. 3 , e278 (2013). [[Full text]][1] [1]: http://www.nature.com/tp/journal/v3/n7/full/tp201347a.html

Neuroimmunology The causes of autism spectrum disorder (ASD) are complex and not entirely clear. Alterations in the mother's immune system during pregnancy, especially during key early periods of fetal neurodevelopment, may play a role. Choi et al. provided infectious or inflammatory stimuli to pregnant mice, which resulted in of spring exhibiting behaviors reminiscent of ASD (see the Perspective by Estes and McAllister). A subset of T helper cells that make the cytokine interleukin-17a in the mothers caused cortical defects and associated ASD behaviors in offspring. Therapeutic targeting of interleukin-17a during gestation reduced ASD symptoms in offspring. Science , this issue p. [933][1]; see also p. [919][2] [1]: /lookup/doi/10.1126/science.aad0314 [2]: /lookup/doi/10.1126/science.aaf2850

As parents, we often have big dreams for our children’s future. However, when parents are told their child has autism—a neurodevelopmental disorder characterized by social, cognitive, and communication difficulties—the questions they ask are: Will my child speak? Will I be able to have a close relationship with my child? Will my child be able to live independently as an adult? A recent U.S. Centers for Disease Control and Prevention report estimates that in 2008, 1 in 88 children received the diagnosis of autism, and that the incidence of autism diagnosis is on the rise. In response to this growing public health concern, scientists have been searching for the causes of autism and ways to prevent and treat this disease. A recent study identified a deletion of exon 2 in the gene encoding trimethyllysine hydroxylase epsilon (TMLHE) in a proband with autism. This gene maps to the X chromosome and encodes the first enzyme in the carnitine biosynthesis pathway. In new work, Celestine-Soper et al. now investigate the possible association of nondysmorphic (milder end of spectrum) autism with TMLHE mutations. They used a PCR assay to study 3813 DNA samples from simplex (one affected male) and multiplex (male-male affected sibling pairs) families and compared them with 8787 DNA samples from related unaffected fathers and unrelated healthy male controls. TMLHE deficiency was 2.85-fold more frequent in probands from multiplex families as compared with controls ( P = 0.023). Six of seven autistic male siblings of probands in these families had the deletion, suggesting that TMLHE deficiency is a risk factor in some cases of nondysmorphic autism (meta-analysis P = 0.0037). This association was not observed in simplex families. Although further replication studies are needed to confirm these findings, the new work suggests that defects in carnitine metabolism may somehow be involved in an increased risk for autism. A big question posed by the authors is whether the risk for autism may be modified by dietary intake of carnitine—a nutrient mostly found in red meat and eggs—during the first few years of life, when children may not consume adequate amounts of these foods. Although much more work is needed, the study by Celestino-Soper et al. provides a new target for autism researchers to start investigating. P. B. S. Celestino-Soper et al. , A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism. Proc. Natl. Acad. Sci. U.S.A ., 7 May 2012 (10.1073/pnas.1120210109). [[Abstract]][1] [1]: http://www.pnas.org/content/early/2012/05/01/1120210109.full.pdf+html

Autism has attracted enormous attention in recent years primarily because of the high incidence and the impact it has on patients' lives and their families, given its medical, social, financial, and emotional burdens ( 1 , 2 ). There is growing acceptance that the incidence and prevalence of autism have dramatically increased over the past 20 years ( 3 ), although some of the increase relates to changing diagnostic terminology and criteria. The use of DNA microarrays and exome sequencing to detect pathological copy number variants (CNVs) and point mutations, respectively, is making progress in identifying genetic causes of autism. The recent confirmation that paternal age is a risk factor for autism relates to the occurrence of de novo point mutations that can now be discovered through next-generation sequencing ( 4 ). However, for virtually all of the pathological CNVs and point mutations causing autism, there is no definitive or curative therapy, although CNVs can be detected using invasive prenatal diagnosis. On page 394 of this issue, Novarino et al. ( 5 ) use exome sequencing in consanguineous families to discover an inborn metabolic error associated with autism, epilepsy, and intellectual disability, in which the clinical manifestations are likely to be treatable or, even better, preventable.