1. Elder JH. {{The gluten-free, casein-free diet in autism: an overview with clinical implications}}. {Nutr Clin Pract};2008 (Dec-2009 Jan);23(6):583-588.
The prevalence of classic autism and autism spectrum disorder (ASD) appears to be on the rise, and to date, there remains no clear etiology or cure. Out of desperation, many families are turning to new therapies and interventions discovered through various media sources and anecdotal reports from other parents. Unfortunately, many of these newer, well-publicized interventions have little empirical support. One of the most popular yet currently scientifically unproven interventions for ASD is the gluten-free, casein-free (GFCF) diet. Clinicians working with families of individuals with ASD are often asked for advice and find themselves unable to offer the most up-to-date and scientifically credible information. This article provides an overview of ASD and the GFCF diet, a summary and critique of current research findings, recommendations for future research, and practical advice for families to use in deciding if a trial of the GFCF diet is in the best interest of their child and family.
2. Fichou Y, Nectoux J, Bahi-Buisson N, et al. {{The first missense mutation causing Rett syndrome specifically affecting the MeCP2_e1 isoform}}. {Neurogenetics};2008 (Nov 26)
We report the identification of the first de novo mutation at a highly conserved residue within the polyalanine stretch in the N-terminal region of the brain-dominant protein isoform MeCP2_e1 in a girl with classical Rett syndrome. The missense mutation, p.Ala2Val, leads to severe developmental delay, microcephaly, no language, severe epilepsy, and cognitive impairment. To evaluate the pathogenic potentials of the MECP2 mutation specific to the MeCP2_e1 isoform detected in this patient, full-length wild-type and mutated cDNAs were cloned in eukaryotic expression vectors to generate a fusion protein with c-myc, and constructs were transfected in COS7 cells. In vitro studies demonstrated that, like wild-type MeCP2e_1, the N-terminal mutant is localized in the nucleus. Neither transcriptional nor translational effect on the MeCP2_e2 isoform was observed in fibroblasts from the p.Ala2Val patient, suggesting that MeCP2_e1 is involved in other functional process. These data suggest the important involvement of the N-terminus in the function of MeCP2 protein, and provide further evidence for the major impact of a specific MeCP2e_1 deficiency in the development of intellectual processing.
3. Goday P. {{Whey watchers and wheat watchers: the case against gluten and casein in autism}}. {Nutr Clin Pract};2008 (Dec-2009 Jan);23(6):581-582.
4. Vernes SC, Newbury DF, Abrahams BS, et al. {{A Functional Genetic Link between Distinct Developmental Language Disorders}}. {N Engl J Med};2008 (Nov 27);359(22):2337-2345.
BACKGROUND: Rare mutations affecting the FOXP2 transcription factor cause a monogenic speech and language disorder. We hypothesized that neural pathways downstream of FOXP2 influence more common phenotypes, such as specific language impairment. METHODS: We performed genomic screening for regions bound by FOXP2 using chromatin immunoprecipitation, which led us to focus on one particular gene that was a strong candidate for involvement in language impairments. We then tested for associations between single-nucleotide polymorphisms (SNPs) in this gene and language deficits in a well-characterized set of 184 families affected with specific language impairment. RESULTS: We found that FOXP2 binds to and dramatically down-regulates CNTNAP2, a gene that encodes a neurexin and is expressed in the developing human cortex. On analyzing CNTNAP2 polymorphisms in children with typical specific language impairment, we detected significant quantitative associations with nonsense-word repetition, a heritable behavioral marker of this disorder (peak association, P=5.0×10(-5) at SNP rs17236239). Intriguingly, this region coincides with one associated with language delays in children with autism. CONCLUSIONS: The FOXP2-CNTNAP2 pathway provides a mechanistic link between clinically distinct syndromes involving disrupted language. Copyright 2008 Massachusetts Medical Society.
