Extending the spectrum of Ellis van Creveld syndrome: a large family with a mild mutation in the EVC gene

<p>Abstract</p> <p>Background</p> <p>Ellis-van Creveld (EvC) syndrome is characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails and teeth and is inherited in an autosomal recessive pattern. We report a family with complex septal cardiac defects, rhizomelic limb shortening, and polydactyly, without the typical lip, dental, and nail abnormalities of EvC. The phenotype was inherited in an autosomal recessive pattern, with one instance of pseudodominant inheritance.</p> <p>Methods</p> <p>Because of the phenotypic overlap with EvC, microsatellite markers were used to test for linkage to the <it>EVC/EVC2 </it>locus. The results did not exclude linkage, so samples were sequenced for mutations.</p> <p>Results</p> <p>We identified a c.1868T>C mutation in <it>EVC</it>, which predicts p.L623P, and was homozygous in affected individuals.</p> <p>Conclusion</p> <p>We conclude that this <it>EVC </it>mutation is hypomorphic and that such mutations can cause a phenotype of cardiac and limb defects that is less severe than typical EvC. <it>EVC </it>mutation analysis should be considered in patients with cardiac and limb malformations, even if they do not manifest typical EvC syndrome.</p

Extending the spectrum of Ellis van Creveld syndrome: a large family with a mild mutation in the EVC gene

<p>Abstract</p> <p>Background</p> <p>Ellis-van Creveld (EvC) syndrome is characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails and teeth and is inherited in an autosomal recessive pattern. We report a family with complex septal cardiac defects, rhizomelic limb shortening, and polydactyly, without the typical lip, dental, and nail abnormalities of EvC. The phenotype was inherited in an autosomal recessive pattern, with one instance of pseudodominant inheritance.</p> <p>Methods</p> <p>Because of the phenotypic overlap with EvC, microsatellite markers were used to test for linkage to the <it>EVC/EVC2 </it>locus. The results did not exclude linkage, so samples were sequenced for mutations.</p> <p>Results</p> <p>We identified a c.1868T>C mutation in <it>EVC</it>, which predicts p.L623P, and was homozygous in affected individuals.</p> <p>Conclusion</p> <p>We conclude that this <it>EVC </it>mutation is hypomorphic and that such mutations can cause a phenotype of cardiac and limb defects that is less severe than typical EvC. <it>EVC </it>mutation analysis should be considered in patients with cardiac and limb malformations, even if they do not manifest typical EvC syndrome.</p

A Comparative Molecular Dynamics Study of Methylation State Specificity of JMJD2A

Histone modifications have great importance in epigenetic regulation. JMJD2A is a histone demethylase which is selective for di- and trimethyl forms of residues Lys9 and Lys36 of Histone 3 tail (H3K9 and H3K36). We present a molecular dynamics simulations of mono-, di- and trimethylated histone tails in complex with JMJD2A catalytic domain to gain insight into how JMJD2A discriminates between the methylation states of H3K9. The methyl groups are located at specific distances and orientations with respect to Fe(II) in methylammonium binding pocket. For the trimethyllysine the mechanism which provides the effectual orientation of methyl groups is the symmetry, whereas for the dimethyllysine case the determining factors are the interactions between methyllysine head and its environment and subsequently the restriction on angular motion. The occurrence frequency of methyl groups in a certain proximity of Fe(II) comes out as the explanation of the enzyme activity difference on di- and tri-methylated peptides. Energy analysis suggests that recognition is mostly driven by van der Waals and followed by Coulombic interactions in the enzyme-substrate interface. The number (mono, di or tri) and orientations of methyl groups and water molecules significantly affect the extent of van der Waals interaction strengths. Hydrogen bonding analysis suggests that the interaction between JMJD2A and its substrates mainly comes from main chain-side chain interactions. Binding free energy analysis points out Arg8 as an important residue forming an intra-substrate hydrogen bond with tri and dimethylated Lys9 of the H3 chain. Our study provides new insights into how JMJD2A discriminates between its substrates from both a structural and dynamical point of view

Optimal Pretreatment System of Flowback Water from Shale Gas Production

Shale gas has emerged as a potential resource to transform the global energy market. Nevertheless, gas extraction from tight shale formations is only possible after horizontal drilling and hydraulic fracturing, which generally demand large amounts of water. Part of the ejected fracturing fluid returns to the surface as flowback water, containing a variety of pollutants. For this reason, water reuse and water recycling technologies have received further interest for enhancing overall shale gas process efficiency and sustainability. Water pretreatment systems (WPSs) can play an important role for achieving this goal. This paper introduces a new optimization model for WPS simultaneous synthesis, especially developed for flowback water from shale gas production. A multistage superstructure is proposed for the optimal WPS design, including several water pretreatment alternatives. The mathematical model is formulated via generalized disjunctive programming (GDP) and solved by re-formulation as a mixed-integer nonlinear programming (MINLP) problem, to minimize the total annualized cost. Hence, the superstructure allows identifying the optimal pretreatment sequence with minimum cost, according to inlet water composition and wastewater-desired destination (i.e., water reuse as fracking fluid or recycling). Three case studies are performed to illustrate the applicability of the proposed approach under specific composition constraints. Thus, four distinct flowback water compositions are evaluated for the different target conditions. The results highlight the ability of the developed model for the cost-effective WPS synthesis, by reaching the required water compositions for each specified destination

Distribution of angiotensin-1 converting enzyme insertion/deletion and α-actinin-3 codon 577 polymorphisms in Turkish male soccer players

Angiotensin-1 converting enzyme (ACE) gene and α-actinin-3 (ACTN3) gene polymorphisms are considered to be the most important candidate genes for genetic predisposition to human athletic performance. In the present study, we aimed to analyze the distribution of ACE and ACTN3 polymorphisms for the first time in male Turkish soccer players. In this prospective study, our cohort consisted of 25 professional players, all with Turkish ancestry. Polymerase chain reaction (PCR)-restriction length polymorphism was used for the characterization of the genotype of ACTN3 and single PCR for ACE . For ACE genotype, 16%, 44%, and 40% of the players had insertion/insertion (II), insertion/deletion (ID), and deletion/deletion (DD) genotypes, respectively, whereas 20% had XX, 36% had RX, and 44% had RR genotypes for ACTN3 . When we examined the allelic percentages, for ACE , D allele was recorded as 62 and I as 38, and for ACTN3 , R allele was 62 and X was 38. Our results were in agreement with the previous reports, indicating the presence of ACTN3 D and ACE X allele in soccer players. We suggest that ACE and ACTN3 genotypes are important biomarkers for genetic counseling for the individuals who are prone to be successful soccer players

Prognostic Value of CYP1A2 (rs2069514 and rs762551) Polymorphisms in COVID-19 Patients

The aim of the study was to examine the genotype-allele determination of CYP1A2 rs2069514 and rs762551 polymorphisms in patients with mild and severe COVID-19 and to determine their effectiveness as prognostic criteria in COVID-19. The study consists of 60 patients who were hospitalized in intensive care or outpatient treatment due to COVID-19 in Istanbul NP Brain Hospital between 2020–2021. Genotyping was conducted by Real-Time PCR. Age (p<0.001); chronic disease (p=0.002); cardiovascular disease (p=0.004); respiratory distress (p<0.001); neurological disease (p=0.004); fatigue (p=0.048); loss of taste and smell (p=0.003); nausea/vomiting (p=0.026); intubated (p<0.001); ground glass image (p<0.001) and CYP1A2 genotypes (p<0.001) showed a statistically significant difference between patients with and without intensive care admission. According to multivariate logistic regression analysis, CYP1A2 *1A/*1C + *1C/*1C genotypes (OR:5.23 95% CI: 1.22–22.36; p=0.025), chronic disease (OR:4.68 95% CI:1.14–19.15; p=0.032) or patients at 65 years or older (OR:5.17, 95%CI:1.26–21.14; p=0.022) increased the risk of admission to the intensive care unit. According to our results, we strongly suggest considering the CYP1A2 rs2069514 and rs762551 polymorphisms as important predictors of Intensive Care Unit admission in patients with COVID-19, and we also suggest that genotype results will guide clinicians for the benefit and the efficiency of the treatment