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Coffin‐Siris syndrome (CSS, OMIM#135900) is a rare congenital disorder associated with neurodevelopmental and dysmorphic features. The primary cause of CSS is pathogenic variants in any of 9 BAF chromatin‐remodeling complex encoding genes or the genes SOX11 and PHF6. Herein, we performed whole‐exome sequencing (WES) and a series of analyses of growth‐related, auditory, and radiological findings in two probands with syndromic sensorineural hearing loss and inner ear malformations who exhibited distinctive facial features, intellectual disability, growth retardation, and fifth finger malformation. Two de novo variants in the SOX11 gene (c.148A>C:p.Lys50Asn; c.811_814del:p.Asn271Serfs*10) were detected in these probands and were identified as pathogenic variants as per ACMG guidelines. These probands were diagnosed as having CSS based upon clinical and genetic findings. This is the first report of CSS caused by variants in SOX11 gene in Chinese individuals. Deleterious SOX11 variants can result in sensorineural hearing loss with inner ear malformation, potentially extending the array of phenotypes associated with these pathogenic variants. We suggest that both genetic and clinical findings be considered when diagnosing syndromic hearing loss. [ABSTRACT FROM AUTHOR]

The methylmercury ion (C[H.sub.3][Hg.sup.+]) demonstrated a high efficiency for directly labeling peptide/protein based on its specific and strong interaction with the sulfhydryl(s) in the peptide/protein and because of its smallest size among monofunctional organic mercurials studied, including methylmercury, ethylmercury, 4-(hydroxymercuric)benzoic acid, and 2,7-dibromo-4-hydroxymercurifluoresceine disodium. A simple 1:1 stoichiometry between C[H.sub.3][Hg.sup.+] and sulthydryl, confirmed with electrospray ionization-mass spectrometry (ESI-MS) and matrix-assisted laser desorption ionization-time-of-flight-mass spectrometry (MALDI-TOFMS) studies, made it easy to calibrate the stoichiometry of Hg in the peptide/protein. In order to avoid the direct use of the harmful C[H.sub.3][Hg.sup.+], in this study a C[H.sub.3][Hg.sup.+]-equivalent tag, methylmercurithiosalicylate (C[H.sub.3]Hg-THI), and its [sup.204]Hg-enriched homologue (C[H.sub.3][sup.204]Hg-THI) were synthesized, and then C[H.sub.3][Hg.sup.+] and/or C[H.sub.3][sup.204][Hg.sup.+] released from C[H.sub.3]Hg-THI and/or C[H.sub.3]Hg-THI in solution were utilized to demonstrate the dynamic labeling of glutathione (GSH) and two model proteins, [beta]-lactoglobulin (BLG) and ovalbumin (OVA), for the first time. Furthermore, the C[H.sub.3][sup.204]HgTHI isotopical labeled GSH, BLG, and OVA standards (C[H.sub.3][sup.204]Hg-GSH, C[H.sub.3][sup.204]Hg-BLG, and C[H.sub.3][sup.204]Hg-OVA) were used to demonstrate the feasibility of absolute peptide/protein quantification using label-specific isotope dilution inductively coupled plasma mass spectrometry (ICPMS). On the basis of the accurate and sensitive determination of Hg using ICPMS, the detection limits of GSH, BLG, and OVA could reach 45.4, 45.4, and 15.1 pmol [L.sup.-1], respectively, suggesting the possibility for low-abundance peptide/protein quantification alongside the surefire quantification of moderate and highly abundant peptide/protein. 10.1021/ac902902y

Quantitative proteomics requires novel analytical methodology to fill the gap related to absolute protein abundance in different physiological conditions. In this paper, we demonstrate a proof-of-concept study for absolute protein quantification. 1,4,7,10-Tetrvazacyclododecane-1,4,7-trisacetic acid-10-maleimidocthylacetamide (MMA-DOTA) loaded with Eu was used to label lysozyme, insulin, and ribonuclease A, and they were subsequently quantified using HPLC coupled with [sup.153]Eu species-unspecific isotope dilution inductively coupled plasma mass spectrometry (ICPMS). Labeling procedures were optimized using electrospray ionization mass spectrometry (ESI-MS) based on the labeling efficiency and specificity of the three intact proteins, which suggested that 10-fold or higher MMA-DOTA to cysteine sulphydryl rates at pH from 6.8 to 7.6 and 47[degrees]C for 40 min were optimal conditions for the conjugation of the reduced-form proteins and that a 5-fold excess of Eu with respect to the DOTA present in the MMA-DOTA-conjugated proteins and pH 5.8 are optimal for Eu labeling. Subsequently, these three MMA-DOTA-Eu-labeled proteins were digested with trypsin, and the tryptic peptides were quantified via HPLC coupled with [sup.153]Eu species-unspecific isotope dilution ICPMS. The results for the protein studied indicated that not only could 100% digestion efficiency not be achieved but also the resulting peptides needed a chromatographic separation at higher resolution. On the other hand, the labeled intact proteins were quantified without tryptic digestion. The average recovery was found to be 97.9% in six independent experiments, and the precision was evaluated to be 5.8% at the 10 pmol [L.sup.-1] level. The detection limits (30) were determined to be 0.819, 1.638, and 0.819 fmol for lysozyme, the A chain of insulin, and ribonuclease A, respectively, using ICPMS with a normal concentric pneumatic nebulizer. These results demonstrated that high-quality absolute protein quantification could be achieved through labeling the intact proteins but not the tryptic peptides, implying that intact proteins may be more feasible and practical targets than tryptic peptides for ICPMS-based absolute protein quantification. 10.1021/ac902163x

An alternative thermodiffusion interface (TDI) was designed and constructed for the effective online coupling of capillary gas chromatography (cGC) and inductively coupled plasma mass spectrometry (ICPMS). [Pb.sup.2+], [([CH.sub.3]).sub.3][Pb.sup.+], [([C.sub.2] [H.sub.5]).sub.3][Pb.sup.2+], [Hg.sup.2+], [CH.sub.3][Hg.sup.+] and [C.sub.2][H.sub.5][Hg.sup.+] were derived as Pb[([C.sub.4] [H.sub.9]).sub.4], [([CH.sub.3]).sub.3]Pb[C.sub.4][H.sub.9], [(C.sub.2] [H.sub.5]).sub.3]Pb[C.sub.4][H.sub.9], [([C.sub.4][H.sub.9]).sub.2]Hg, [CH.sub.3]Hg[C.sub.4][H.sub.9], and [C.sub.2][H.sub.5]Hg[C.sub.4] [H.sub.9] when butyl magnesium bromide was employed as a derivatization reagent for a proof-of-concept study, avoiding the loss of their species specific information. All these derivatives together with the neutral fully saturated [([CH.sub.3]).sub.4]Pb and [([C.sub.2] [H.sub.5]).sub.4]Pb could be quantitatively separated within 7 min using a 15 m long capillary column, allowing the determination and speciation of organic and inorganic Pb and Hg species in a single run. The method detection limits (3[sigma]) for [Me.sub.4]Pb, [Et.sub.4]Pb, [Me.sub.3][Pb.sup.3+], [Pb.sup.2+], Me[Hg.sup.+], Et[Hg.sup.+], and [Hg.sup.2+] are 0.07, 0.06, 0.04, 7.0, 0.09, 0.1, and 0.2 pg [g.sup.-1], respectively. Moreover, tri-n-propyl-lead chloride was synthesized and used as an alternative internal standard for the accurate and simultaneous speciation analysis of Pb and Hg in complicated environmental and biological samples for the first time. This cGC-TDI-ICPMS method was validated by analyzing Pb and Hg species in certified reference materials and then was applied to simultaneous speciation analysis of Pb and Hg in reallife samples. It is expected that these approaches can be extended to the speciation of other organometallic compounds after suitable modifications and so will aid in monitoring the occurrence, pathways, toxicity, and/or biological effects of these compounds in the environment and in organisms.