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Advanced cholestatic liver disease is a leading referral to pediatric liver transplant centers. Recent advances in the genetic classification of this group of disorders promise a highly personalized management although the genetic heterogeneity also poses a diagnostic challenge. Using a next-generation sequencing-based multi-gene panel, we performed retrospective analysis of 98 pediatric patients who presented with advanced cholestatic liver disease. A likely causal mutation was identified in the majority (61%), spanning many genes including ones that have only rarely been reported to cause cholestatic liver disease, e.g. TJP2 and VIPAS39. We find no evidence to support mono-allelic phenotypic expression in the carrier parents despite the severe nature of the respective mutations, and no evidence of oligogenicity. The high-carrier frequency of the founder mutations identified in our cohort (1 in 87) suggests a minimum incidence of 1:7246, an alarmingly high disease burden that calls for the primary prevention through carrier screening. [ABSTRACT FROM AUTHOR]

Hypertriglyceridemia ( hTG) is a lipid disorder, resulting from an elevation in triglyceride levels, with a strong genetic component. It constitutes a significant risk factor for coronary artery disease ( CAD), a leading cause of death worldwide. In this study, we performed a common variant association study for hTG in ethnic Saudi Arabs. We genotyped 5501 individuals in a two-phase experiment using Affymetrix Axiom® Genome-Wide CEU 1 Array (Affymetrix, Santa Cruz, CA) that contains a total of 587,352 single nucleotide polymorphisms ( SNPs). The lead variant was the rs1558861 [1.99 (1.73-2.30); p = 7.37 × 10−22], residing on chromosome (chr) 11 at the apolipoprotein A-I/A-5 ( APOA1 / APOA5) locus. The rs780094 [1.34 (1.21-1.49); p = 8.57 × 10−8] on chr 2 at the glucokinase regulatory protein ( GCKR) locus was similarly significantly associated, while the rs10911205 [1.29 (1.16-1.44); p = 3.52 × 10−6] on chr1 at the laminin subunit gamma-1 ( LAMC1) locus showed suggestive association with disease. Furthermore, the rs17145738 [0.68 (0.60-0.77); p = 6.69 × 10−9] on chr7 at the carbohydrate-responsive element-binding protein-encoding ( MLXIPL) gene locus displayed significant protective characteristics, while another variant rs6982502 [0.76 (0.68-0.84); p = 5.31 × 10−7] on chr8 showed similar but weaker properties. These findings were replicated in 317 cases vs 1415 controls from the same ethnic Arab population. Our study identified several variants across the human genome that are associated with hTG in ethnic Arabs. [ABSTRACT FROM AUTHOR]

The genetic susceptibility to acquiring low high density lipoprotein-cholesterol ( LHDLC) levels is not completely elucidated yet. In this study, we performed a common variant association study for harboring this trait in ethnic Arabs. We employed the Affymetrix high-density Axiom Genome-Wide ASI Array (Asian population) providing a coverage of 598,000 single nucleotide variations ( SNPs) to genotype 5495 individuals in a two-phase study involving discovery and validation sets of experiments. The rs1800775 [1.31 (1.22-1.42); p = 3. 41E-12] in the CETP gene and rs359027 [1.26 (1.16-1.36); p = 2. 55E-08] in the LMCD1 gene were significantly associated with LHDLC levels. Furthermore, rs3104435 [1.26 (1.15-1.38); p = 1. 19E-06] at the MATN1 locus, rs9835344 [1.16 (1.08-1.26); p = 8. 75E-06] in the CNTN6 gene, rs1559997 [1.3 (1.14-1.47); p = 9. 48E-06] in the SDS gene and rs1670273 [1.2 (1.1-1.31); p = 4. 81E-06] in the DMN/ SYNM gene exhibited suggestive association with the disorder. Seven other variants including rs1147169 in the PLCL1 gene, rs10248618 in the DNAH11, rs476155 in the GLIS3, rs7024300 in the ABCA1, intergenic rs10836699, rs11603691 in P2RX3 and rs750134 in CORO1C gene exhibited borderline protective properties. Validation and joint meta-analysis resulted in rs1800775, rs3104435 and rs359027 retaining their predisposing properties, while rs10836699 and rs11603691 showed protective properties. Our data show several predisposing variants across the genome for LHDLC levels in ethnic Arabs. [ABSTRACT FROM AUTHOR]

Clozapine is an atypical antipsychotic used for treatment resistant schizophrenia. Its potential to induce agranulocytosis is well known but it can also cause myocarditis. Clozapine is the only antipsychotic known to induce this side effect, typically early in the treatment, and literature is scarce on this condition. We are presenting a case report of a 21-year-old schizophrenic male who developed myocarditis within 3 weeks of starting on clozapine for his treatment resistant psychosis. We then aim to review some of the available literature and raise awareness among physicians as this condition can potentially be fatal if not detected early. [ABSTRACT FROM AUTHOR]

The crystal structure of Cd3As2 is redetermined by single crystal XRD. [ABSTRACT FROM AUTHOR]

A mixture of α-Ag0.79VS2 and β-Ag0.79VS2 is prepared by solid state reaction of a stoichiometric mixture of Ag, V, and S powder (evacuated quartz tube, 750 °C, 6 d). [ABSTRACT FROM AUTHOR]

Layered polycrystalline Na3Ni2BiO6 is prepared by firing stoichiometric amounts of Na2CO3, NaBiO3, and NiO with a 3% excess of Na for compensating volatilization losses (alumina boat, 700 °C, 8 h, flowing O2). [ABSTRACT FROM AUTHOR]