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The beta-actin gene encodes 1 of 6 different actin proteins. De novo heterozygous missense mutations in ACTB have been identified in patients with Baraitser-Winter syndrome (BRWS) and also in patients with developmental disorders other than BRWS, such as deafness, dystonia, and neutrophil dysfunction. We describe 2 different novel de novo missense ACTB mutations, c.208C>G (p.Pro70Ala) and c.511C>T (p.Leu171Phe), found by trio exome sequencing analysis of 2 unrelated patients: an 8-year-old boy with a suspected BRWS and a 4-year-old girl with unclear developmental disorder. The mutated residue in the first case is situated in the actin H-loop, which is involved in actin polymerization. The mutated residue in the second case (p.Leu171Phe) is found at the actin barbed end in the W-loop, important for binding to profilin and other actin-binding molecules. While the boy presented with a typical BRWS facial appearance, the girl showed facial features not recognizable as a BRWS gestalt as well as ventricular arrhythmia, cleft palate, thrombocytopenia, and gray matter heterotopia. We reviewed previously published ACTB missense mutations and ascertained that a number of them do not cause typical BRWS. By comparing clinical and molecular data, we speculate that the phenotypic differences found in ACTB missense mutation carriers might supposedly be dependent on the conformational change of ACTB.

DNA immunoprecipitation followed by sequencing (DIP-seq) is a common enrichment method for profiling DNA modifications in mammalian genomes. However, the results of independent DIP-seq studies often show considerable variation between profiles of the same genome and between profiles obtained by alternative methods. Here we show that these differences are primarily due to the intrinsic affinity of IgG for short unmodified DNA repeats. This pervasive experimental error accounts for 50–99% of regions identified as ‘enriched’ for DNA modifications in DIP-seq data. Correction of this error profoundly altered DNA-modification profiles for numerous cell types, including mouse embryonic stem cells, and subsequently revealed novel associations among DNA modifications, chromatin modifications and biological processes. We conclude that both matched input and IgG controls are essential in order for the results of DIP-based assays to be interpreted correctly, and that complementary, non-antibody-based techniques should be used to validate DIP-based findings to avoid further misinterpretation of genome-wide profiling data. Reanalysis of DNA-immunoprecipitation-based data shows that modification-specific antibodies bind unmodified short tandem repeats, and IgG controls are needed to avoid false positives.

Tris(dialkylamino)benzylphosphoniumbromide [(R2N)3PCH2C6H5]+Br–(R: Me, Et, n‐Pr, n‐Bu) sind durch Reaktion der entsprechenden Tris(dialkylamino)phosphine mit Benzylbromid in hohen Ausbeuten (Ausnahme R = n‐Bu) erhältlich. Aus Acetonitril oder Methylenchlorid fallen die Verbindungen nach Zusatz von Diethylether in Form farbloser Kristalle aus. Der äquimolare Umsatz der Tris(dialkylamino)benzylphosphonium‐bromide mit Brom führt in glatter Reaktion zu den entsprechenden Tris(dialkylamino)benzylphosphonium‐tribromiden, die aus den genannten Lösemitteln nach Zusatz von Diethylether in Form orange‐roter Kristalle ausfallen. Die Kristallstrukturanalysen der Tris(dialkylamino)benzylphosphoniumbromide bzw. ‐tribromide zeigten, daß die jeweiligen dreifach koordinierten N‐Atome in allen untersuchten Verbindungen nahezu planar konfiguriert sind.

AbstractAs part of our studies on the crystal structures of phosphonium halides [1] we haveprepared various phosphonium bromides. These can been obtained by the reaction of a phosphine with aryl or alkyl bromides in acetonitrile or methylene chloride:

The phosphonium salts have been prepared by the reaction of triphenylphosphine with the corresponding halomethanes (eq. (1)) and bromine (eq.(2)), respectively.