De novo triplication of 11q12.3 in a patient with developmental delay and distinctive facial features

BACKGROUND: Triplication is a rare chromosomal anomaly. We identified a de novo triplication of 11q12.3 in a patient with developmental delay, distinctive facial features, and others. In the present study, we discuss the mechanism of triplications that are not embedded within duplications and potential genes which may contribute to the phenotype. RESULTS: The identified triplication of 11q12.3 was 557 kb long and not embedded within the duplicated regions. The aberrant region was overlapped with the segment reported to be duplicated in 2 other patients. The common phenotypic features in the present patient and the previously reported patient were brain developmental delay, finger abnormalities (including arachnodactuly, camptodactyly, brachydactyly, clinodactyly, and broad thumbs), and preauricular pits. CONCLUSIONS: Triplications that are not embedded within duplicated regions are rare and sometimes observed as the consequence of non-allelic homologous recombination. The de novo triplication identified in the present study is novel and not embedded within the duplicated region. In the 11q12.3 region, many copy number variations were observed in the database. This may be the trigger of this rare triplication. Because the shortest region of overlap contained 2 candidate genes, STX5 and CHRM1, which show some relevance to neuronal functions, we believe that the genomic copy number gains of these genes may be responsible for the neurological features seen in these patients

A Novel Signaling Pathway Mediated by the Nuclear Targeting of C-Terminal Fragments of Mammalian Patched 1

Background: Patched 1 (Ptc1) is a polytopic receptor protein that is essential for growth and differentiation. Its extracellular domains accept its ligand, Sonic Hedgehog, while the function of its C-terminal intracellular domain is largely obscure. Principal Findings: In this study, we stably expressed human Ptc1 protein in HeLa cells and found that it is subjected to proteolytic cleavage at the C-terminus, resulting in the generation of soluble C-terminal fragments. These fragments accumulated in the nucleus, while the N-terminal region of Ptc1 remained in the cytoplasmic membrane fractions. Using an anti-Ptc1 C-terminal domain antibody, we provide conclusive evidence that C-terminal fragments of endogenous Ptc1 accumulate in the nucleus of C3H10T1/2 cells. Similar nuclear accumulation of endogenous C-terminal fragments was observed not only in C3H10T1/2 cells but also in mouse embryonic primary cells. Importantly, the C-terminal fragments of Ptc1 modulate transcriptional activity of Gli1. Conclusions: Although Ptc1 protein was originally thought to be restricted to cell membrane fractions, our findings sugges

Uranium XAFS analysis of kidney from rats exposed to uranium

AbstractThe kidney is the critical target of uranium exposure because uranium accumulates in the proximal tubules and causes tubular damage, but the chemical nature of uranium in kidney, such as its chemical status in the toxic target site, is poorly understood. Micro-X-ray absorption fine structure (μXAFS) analysis was used to examine renal thin sections of rats exposed to uranyl acetate. The U LIII-edge XANES spectra of bulk renal specimens obtained at various toxicological phases were similar to that of uranyl acetate: their edge position did not shift compared with that of uranyl acetate (17.175 keV) although the peak widths for some kidney specimens were slight narrowed. μXAFS measurements of spots of concentrated uranium in the micro-regions of the proximal tubules showed that the edge jump slightly shifted to lower energy. The results suggest that most uranium accumulated in kidney was uranium (VI) but a portion might have been biotransformed in rats exposed to uranyl acetate