Bondeson, M.-L., Dahl, N., Malmgren, H., Kleijer, W. J., Tonnesen, T., Carlberg, B.-M., Pettersson, U. In 2 of 22 aldosterone-producing adrenal adenomas (APAs) from unrelated patients with primary hyperaldosteronism (613677), Choi et al. (2011) identified a somatic G-to-A transition at position chr11:126,286,829 in the KCNJ5 gene, resulting in a gly151-to-arg (G151R) substitution. Wilson et al. (1991) found a deletion or gene rearrangement in 7 of 23 patients with mucopolysaccharidosis type II (Hunter syndrome; 309900) of Australian and British origin. In 2 of 14 unrelated German MPS II patients, structural alteration of the IDS gene was found by Southern analysis using an IDS cDNA clone as a probe. In one of these patients, a severely affected male, no Southern fragments were detected.

Sukegawa, K., Song, X.-Q., Masuno, M., Fukao, T., Shimozawa, N., Fukuda, S., Isogai, K., Nishio, H., Matsuo, M., Tomatsu, S., Kondo, N., Orii, T. The G-protein-gated atrial K+ channel I-KACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins. If VWR’s performance of the services is prevented or delayed by any act or omission of the customer, VWR shall without limiting its other rights or remedies, have the right to suspend performance of the services until the customer remedies the position and VWR shall not be liable for any losses or costs arising from such delay. Health, Safety and Liability In a 12-year-old boy with MPS II, Sukegawa et al. (1992) identified a missense mutation in the IDS gene ( 300823.0001). The customer is required to ensure that the use of any products supplied by VWR does not infringe the intellectual property rights of any third party and the customer shall indemnify VWR against any claims made against VWR by any third party in relation to any such infringement or alleged infringement.In a large 4-generation Chinese family with autosomal dominant long QT syndrome mapping to chromosome 11q23.3-q23.4 (LQT13; 613485), Yang et al. (2010) sequenced the candidate gene KCNJ5 and identified heterozygosity for a missense mutation (G387R; 600734.0001) in affected individuals. The mutation, which was not found in 528 ethnically matched controls, was also detected in 2 asymptomatic family members, indicating incomplete penetrance. Patch-clamp studies demonstrated that the mutation has a dominant-negative effect that results in near-complete loss of channel activity compared to wildtype. On termination of the contract for any reason the customer shall immediately pay to VWR all of its outstanding unpaid invoices and interest. Confidentiality The actual shade displayed/printed will depend on your system settings and should therefore be used for guidance only. In a 12-year-old boy with MPS II, Sukegawa et al. (1992) identified a missense mutation in the IDS gene (300823.0001).

In the family with hyperaldosteronism reported by Geller et al. (2008), Choi et al. (2011) identified a missense mutation in the potassium channel gene KCNJ5 at codon 158 (T158A; 600734.0002). This mutation produced increased sodium conductance and caused severe hypertension. Choi et al. (2011) also identified 2 recurrent somatic mutations in and near the selectivity filter of KCNJ5, G151R (600734.0004), and L168R, that were present in 8 of 22 human aldosterone-producing adrenal adenomas studied. These 2 mutations produced increased sodium conductance and cell depolarization, which in adrenal glomerulosa cells produces calcium entry, the signal for aldosterone production and cell proliferation. In a mother and daughter with severe aldosteronism requiring total adrenalectomy, Charmandari et al. (2012) identified heterozygosity for a missense mutation in the KCNJ5 gene (I157S; 600734.0006).Fujian Start Group Co.Ltd signed a letter of intent to acquire 51% stake in Fujian Nebula Big Data Application Service Co., Ltd. from Fujian Big Data Co., Ltd. Kosuga, M., Mashima, R., Hirakiyama, A., Fuji, N., Kumagai, T., Seo, J.-H., Nikaido, M., Saito, S., Ohno, K., Sakuraba, H., Okuyama, T.

Palmieri, G., Capra, V., Romano, G., D'Urso, M., Johnson, S., Schlessinger, D., Morris, P., Hopwood, J., Di Natale, P., Gatti, R., Ballabio, A. Presence of an IDS-related locus (IDS2) in Xq28 complicates the mutational analysis of Hunter syndrome. Scholl et al. (2012) studied 4 unrelated kindreds with very early-onset primary aldosteronism, with all but 1 of the 10 affected members diagnosed before 6 years of age. In 2 of the families, blood pressure was difficult to control, and aldosteronism progressed with age. The 38-year-old proband of the first family presented at 22 months of age with muscle weakness, severe hypokalemia, and hypertension that persisted despite treatment with spironolactone. She underwent removal of a hyperplastic left adrenal gland at 32 months of age, but her symptoms persisted, and the right adrenal gland was removed at 4.3 years of age; both adrenal glands were markedly enlarged and showed hyperplasia of the zona glomerulosa and fasciculata. The bilateral adrenalectomy normalized blood pressure and K+ levels. The proband had 2 affected daughters, both of whom were diagnosed before 2 years of age and had hypertension refractory to spironolactone treatment; both had normalization of blood pressure, potassium, and aldosterone levels after bilateral adrenalectomy. The affected individual in the second family presented at 4 years of age with hypertension, hypokalemia, metabolic alkalosis, and an elevated serum aldosterone level with suppressed plasma renin activity. Ultrasound of the abdomen was normal. She had difficult-to-control hypertension, and was lost to follow-up. In the third and fourth families, spironolactone normalized blood pressure, and there was no progression of disease with age. The proband of the third family was a 38-year-old woman, previously described by Greco et al. (1982), who presented at 26 months of age with hypertension and hyperaldosteronism. Treatment with spironolactone normalized her blood pressure, and she did not have progression of hypertension or growth of the adrenal glands with age; CT scan at age 37 years revealed no adrenal abnormality. She had 2 affected children, both diagnosed before 2 years of age and successfully treated with spironolactone. Her affected father, who was reported by Bartter and Biglieri (1958), had early hypertension and aldosteronism and underwent near-total bilateral adrenalectomy at 14 years of age, before the availability of mineralocorticoid receptor antagonists. The glands were described as histologically normal, and he was normotensive and normokalemic thereafter. The fourth family consisted of a father and son who both presented in the first few years of life with hypertension and elevated aldosterone. The father underwent bilateral adrenalectomy at 6 years of age; the son was successfully treated with spironolactone. In affected members of a large 4-generation Chinese family with autosomal dominant long QT syndrome (LQT13; 613485), Yang et al. (2010) identified heterozygosity for a 1473C-G transversion in the KCNJ5 gene, resulting in a gly387-to-arg (G387R) substitution at a highly conserved residue. The mutation, which was not found in 528 ethnically matched controls, was also detected in 2 asymptomatic family members, indicating incomplete penetrance. Patch-clamp studies in HEK293 cells cotransfected with Kir3.4 and Kir3.1 (KCNJ3; 601534) demonstrated that the mutant has a dominant-negative effect resulting in drastic reduction of inward currents compared to wildtype. In addition, plasma membrane and intracellular expression levels of Kir3.4 and Kir3.1 were markedly reduced in HEK293 cells cotransfected with the mutation compared to wildtype. Caveat to genotype-phenotype correlation in mucopolysaccharidosis type II: discordant clinical severity of R468W and R468Q mutations of the iduronate-2-sulfatase gene.Choi et al. (2011) identified 2 recurrent somatic mutations in and near the selectivity filter of KCNJ5 present in 8 of 22 human aldosterone-producing adrenal adenomas: G151R ( 600734.0004) and L168R. In addition, Choi et al. (2011) identified heterozygosity for a missense mutation in KCNJ5 (T158A; 600734.0002) in a family segregating autosomal dominant hyperaldosteronism type III (HALD3; 613677). This mutation caused increased sodium conductance and severe aldosteronism and massive bilateral adrenal hyperplasia. All intellectual property rights arising out of or in connection with the services shall be owned by VWR. Termination Murthy et al. (2014) analyzed the KCNJ5 gene in 251 patients with apparent sporadic florid primary aldosteronism, and identified 3 heterozygous missense mutations, G247R (rs200170681; 600734.0003), E246K (600734.0007), and R52H (rs144062083). In addition, 12 (5%) of the 251 patients carried the rare SNP E282Q (rs7102584), present at a population frequency of 2% in the 1000 Genomes cohort. Although remote from the KCNJ5 selectivity filter, 3 of the 4 variants (E246K, R52H, and E282Q) were shown to alter inward rectification, conduction of Na+ currents, and angiotensin II (106150)-induced aldosterone release in the H295R cell line, a well-established model for the human zona glomerulosa cell. Results of electrophysiologic analysis of the G247R channel, however, were indistinguishable from those of the wildtype channel. Faust, C. J., Verkerk, A. J. M. H., Wilson, P. J., Morris, C. P., Hopwood, J. J., Oostra, B. A., Herman, G. E. Characterization of the factor deficient in the Hunter syndrome by polyacrylamide gel electrophoresis.

Whitley, C. B., Anderson, R. A., Aronovich, E. L., Crotty, P. L., Anyane-Yeboa, K., Russo, D., Warburton, D. Mechanosensitivity of the cardiac muscarinic potassium channel: a novel property conferred by Kir3.4 subunit. A novel point mutation in the KCNJ5 gene causing primary hyperaldosteronism and early-onset autosomal dominant hypertension. Mutation analysis in the iduronate-2-sulphatase gene in 43 Japanese patients with mucopolysaccharidosis type II (Hunter disease). Perry et al. (2008) identified prominent Girk4 expression mouse hypothalamus, with most pronounced expression in the ventromedial, paraventricular, and arcuate nuclei, neuron populations implicated in energy homeostasis.Customers who exceed their credit limits will be asked to pay in advance for additional products and/or services until the account is settled. Where delivery or performance dates are stated by VWR these are estimates only and time is not of the essence; however, if VWR needs to change such dates it will do so only after providing information to the customer and having regards to the customer’s stated objectives.