Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes

Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable disorder, but specific genetic factors underlying risk remain elusive. To assess the role of structural variation in ADHD, we identified 222 inherited copy number variations (CNVs) within 335 ADHD patients and their parents that were not detected in 2026 unrelated healthy individuals. Although no excess CNVs, either deletions or duplications, were found in the ADHD cohort relative to controls, the inherited rare CNV-associated gene set was significantly enriched for genes reported as candidates in studies of autism, schizophrenia and Tourette syndrome, including A2BP1, AUTS2, CNTNAP2 and IMMP2L. The ADHD CNV gene set was also significantly enriched for genes known to be important for psychological and neurological functions, including learning, behavior, synaptic transmission and central nervous system development. Four independent deletions were located within the protein tyrosine phosphatase gene, PTPRD, recently implicated as a candidate gene for restless legs syndrome, which frequently presents with ADHD. A deletion within the glutamate receptor gene, GRM5, was found in an affected parent and all three affected offspring whose ADHD phenotypes closely resembled those of the GRM5 null mouse. Together, these results suggest that rare inherited structural variations play an important role in ADHD development and indicate a set of putative candidate genes for further study in the etiology of ADHD

Effects of complement regulators bound to Escherichia coli K1 and Group B Streptococcus on the interaction with host cells

Escherichia coli K1 and Group B Streptococcus (GBS) are the most common bacteria that cause meningitis during the neonatal period. Complement, the first line of defence in the host, acts on these bacteria to opsonize with various components of complement for subsequent presentation to phagocytes. To counteract these opsonization effects, E. coli and GBS bind to the complement regulators C4 binding protein and Factor H, respectively. Nonetheless, the deposition of complement components on these two bacteria from neonatal serum and their effect on the host cell interaction is unclear. Here we demonstrated that the deposition of complement proteins from adult serum prevented the invasion of E. coli into human brain microvascular endothelial cells, whereas the invasion of GBS was enhanced. In contrast, treatment with cord serum had no effect on the invasion of both these bacteria. We also examined the effect of the deposited complement proteins on phagocytosis using THP-1 cells and THP-1 cells differentiated into macrophages. Escherichia coli treated with adult serum neither attached nor entered these cells, whereas GBS was phagocytosed and survived efficiently. We further demonstrate that the inhibitory effect of complement proteins is the result of the bound complement inhibitors C4b-binding protein, in the case of E. coli, and Factor H, in the case of GBS. Taken together, these results suggest that E. coli and GBS utilize contrasting mechanisms of complement-mediated interactions with their target cells for successful establishment of disease

Homozygous α-thalassemia in a growth retarded, non-hydropic premature newborn

10.1038/sj.jp.7211873Journal of Perinatology282158-15