Search

Your search keyword '"Janner, Marco"' showing total 49 results
Start Over Author "Janner, Marco"
49 results on '"Janner, Marco"'

1. Clinical and genetic characteristics of a large international cohort of individuals with rare NR5A1/SF-1 variants of sex development

Author

Abali, Saygin, Abali, Zehra Yavas, Akin, Leyla, Almaraz, Maricruz, Audí, Laura, Aydin, Murat, Balsamo, Antonio, Baronio, Federico, Bryce, Jillian, Busiah, Kanetee, Caimari, Maria, Camats-Tarruella, Núria, Campos-Martorell, Ariadna, Castaño, Luis, Casteràs, Anna, Çetinkaya, Semra, Chan, Yee-Ming, Claahsen-van der Grinten, Hedi L., Costa, Ines, Darendeliler, Fatma Feyza, Davies, Justin H., Esteva, Isabel, Fabbri-Scallet, Helena, Finlayson, Courtney A., Garcia, Emilio, Garcia Cuartero, Beatriz, German, Alina, Globa, Evgenia, Guerra-Junior, Gil, Guerrero, Julio, Guran, Tulay, Hannema, Sabine E., Hiort, Olaf, Hirsch, Josephine, Hughes, Leuan, Janner, Marco, Kolesinska, Zofia, Lachlan, Katherine, Lauber-Biason, Anna, Malikova, Jana Krenek, l'Allemand, Dagmar, Lenhnerr-Taube, Nina, Lucas-Herald, Angela, Mammadova, Jamala, MсElreavey, Kenneth, Mericq, Veronica, Mönig, Isabel, Moreno, Francisca, Mührer, Julia, Niedziela, Marek, Nordenstrom, Anna, Orman, Burçe, Poyrazoglu, Sukran, Rial, Jose M., Rutter, Meilan M., Rodríguez, Amaia, Schafer-Kalkhoff, Tara, Sauter, Kay-Sara, Seneviratne, Sumudu Nimali, Sredkova-Ruskova, Maria, Tadokoro-Cuccaro, Rieko, Thankamony, Ajay, Tomé, Mónica, Vela, Amaia, Wasniewska, Malgorzata, Zangen, David, Zelinska, Nataliya, Kouri, Chrysanthi, Sommer, Grit, Martinez de Lapiscina, Idoia, Elzenaty, Rawda Naamneh, Tack, Lloyd J.W., Cools, Martine, Ahmed, S. Faisal, and Flück, Christa E.

Published
2024
Full Text
View/download PDF

5. Clinical and genetic characteristics of a large international cohort of individuals with rare NR5A1/SF-1 variants of sex development

Author

Kouri, Chrysanthi, primary, Sommer, Grit, additional, Martinez de Lapiscina, Idoia, additional, Elzenaty, Rawda Naamneh, additional, Tack, Lloyd J.W., additional, Cools, Martine, additional, Ahmed, S. Faisal, additional, Flück, Christa E., additional, Abali, Saygin, additional, Abali, Zehra Yavas, additional, Akin, Leyla, additional, Almaraz, Maricruz, additional, Audí, Laura, additional, Aydin, Murat, additional, Balsamo, Antonio, additional, Baronio, Federico, additional, Bryce, Jillian, additional, Busiah, Kanetee, additional, Caimari, Maria, additional, Camats-Tarruella, Núria, additional, Campos-Martorell, Ariadna, additional, Castaño, Luis, additional, Casteràs, Anna, additional, Çetinkaya, Semra, additional, Chan, Yee-Ming, additional, Claahsen-van der Grinten, Hedi L., additional, Costa, Ines, additional, Darendeliler, Fatma Feyza, additional, Davies, Justin H., additional, Esteva, Isabel, additional, Fabbri-Scallet, Helena, additional, Finlayson, Courtney A., additional, Garcia, Emilio, additional, Garcia Cuartero, Beatriz, additional, German, Alina, additional, Globa, Evgenia, additional, Guerra-Junior, Gil, additional, Guerrero, Julio, additional, Guran, Tulay, additional, Hannema, Sabine E., additional, Hiort, Olaf, additional, Hirsch, Josephine, additional, Hughes, Leuan, additional, Janner, Marco, additional, Kolesinska, Zofia, additional, Lachlan, Katherine, additional, Lauber-Biason, Anna, additional, Malikova, Jana Krenek, additional, l'Allemand, Dagmar, additional, Lenhnerr-Taube, Nina, additional, Lucas-Herald, Angela, additional, Mammadova, Jamala, additional, MсElreavey, Kenneth, additional, Mericq, Veronica, additional, Mönig, Isabel, additional, Moreno, Francisca, additional, Mührer, Julia, additional, Niedziela, Marek, additional, Nordenstrom, Anna, additional, Orman, Burçe, additional, Poyrazoglu, Sukran, additional, Rial, Jose M., additional, Rutter, Meilan M., additional, Rodríguez, Amaia, additional, Schafer-Kalkhoff, Tara, additional, Sauter, Kay-Sara, additional, Seneviratne, Sumudu Nimali, additional, Sredkova-Ruskova, Maria, additional, Tadokoro-Cuccaro, Rieko, additional, Thankamony, Ajay, additional, Tomé, Mónica, additional, Vela, Amaia, additional, Wasniewska, Malgorzata, additional, Zangen, David, additional, and Zelinska, Nataliya, additional

Published
2024
Full Text
View/download PDF

10. Evidence for protein leverage in a general population sample of children and adolescents

Author

Saner, Christoph, Senior, Alistair M., Zhang, Hanyue, Eloranta, Aino Maija, Magnussen, Costan G., Sabin, Matthew A., Juonala, Markus, Janner, Marco, Burgner, David P., Schwab, Ursula, Haapala, Eero A., Heitmann, Berit L., Simpson, Stephen J., Raubenheimer, David, Lakka, Timo A., Saner, Christoph, Senior, Alistair M., Zhang, Hanyue, Eloranta, Aino Maija, Magnussen, Costan G., Sabin, Matthew A., Juonala, Markus, Janner, Marco, Burgner, David P., Schwab, Ursula, Haapala, Eero A., Heitmann, Berit L., Simpson, Stephen J., Raubenheimer, David, and Lakka, Timo A.

Abstract

Background/Objectives The strong regulation of protein intake can lead to overconsumption of total energy on diets with a low proportion of energy from protein, a process referred to as protein leverage. The protein leverage hypothesis posits that protein leverage explains variation in energy intake and potentially obesity in ecological settings. Here, we tested for protein leverage and the protein leverage hypothesis in children and adolescents. Subjects/Methods A population sample of children, mean (SD) age 7.6 (0.4) years (n = 422), followed up at age 9.8 (0.4) years (n = 387) and at age 15.8 (0.4) years (n = 229), participating for the Physical Activity and Nutrition in Children (PANIC) study. Exposures: 4-day food records-related proportional energy intake of proteins, fats, and carbohydrates. Outcomes: energy intake, body mass index (BMI) z-score and dual-energy X-ray absorptiometry-related energy expenditure. Results Proportional energy intake of proteins was inversely associated with energy intake following power functions at all 3 ages (mean [95%CI] strength of leverage of L = −0.36 [−0.47 to −0.25]; L = −0.26 [−0.37 to −0.15]; L = −0.25 [−0.38 to −0.13]; all P < 0.001). Mixture analysis indicated that variance in energy intake was associated primarily with the proportional intake of energy from proteins, not with either fats or carbohydrates. At all 3 ages, energy intake was not associated with BMI z-score but positively associated with energy expenditure (all P < 0.001). Conclusions This study provides evidence consistent with protein leverage in a population sample of children and adolescents. Increased energy intake on diets with lower protein content was counterbalanced by increased energy expenditure and therefore did not translate into increased adiposity. Introduction, Background/Objectives: The strong regulation of protein intake can lead to overconsumption of total energy on diets with a low proportion of energy from protein, a process referred to as protein leverage. The protein leverage hypothesis posits that protein leverage explains variation in energy intake and potentially obesity in ecological settings. Here, we tested for protein leverage and the protein leverage hypothesis in children and adolescents. Subjects/Methods: A population sample of children, mean (SD) age 7.6 (0.4) years (n = 422), followed up at age 9.8 (0.4) years (n = 387) and at age 15.8 (0.4) years (n = 229), participating for the Physical Activity and Nutrition in Children (PANIC) study. Exposures: 4-day food records-related proportional energy intake of proteins, fats, and carbohydrates. Outcomes: energy intake, body mass index (BMI) z-score and dual-energy X-ray absorptiometry-related energy expenditure. Results: Proportional energy intake of proteins was inversely associated with energy intake following power functions at all 3 ages (mean [95%CI] strength of leverage of L = −0.36 [−0.47 to −0.25]; L = −0.26 [−0.37 to −0.15]; L = −0.25 [−0.38 to −0.13]; all P < 0.001). Mixture analysis indicated that variance in energy intake was associated primarily with the proportional intake of energy from proteins, not with either fats or carbohydrates. At all 3 ages, energy intake was not associated with BMI z-score but positively associated with energy expenditure (all P < 0.001). Conclusions: This study provides evidence consistent with protein leverage in a population sample of children and adolescents. Increased energy intake on diets with lower protein content was counterbalanced by increased energy expenditure and therefore did not translate into increased adiposity.

Published
2023

11. Clinically practical pharmacometrics computer model to evaluate and personalize pharmacotherapy in pediatric rare diseases: application to Graves' disease

Author

Steffens, Britta, primary, Koch, Gilbert, additional, Gächter, Pascal, additional, Claude, Fabien, additional, Gotta, Verena, additional, Bachmann, Freya, additional, Schropp, Johannes, additional, Janner, Marco, additional, l'Allemand, Dagmar, additional, Konrad, Daniel, additional, Welzel, Tatjana, additional, Szinnai, Gabor, additional, and Pfister, Marc, additional

Published
2023
Full Text
View/download PDF

13. Evidence for protein leverage in a general population sample of children and adolescents

Author

Saner, Christoph, primary, Senior, Alistair M., additional, Zhang, Hanyue, additional, Eloranta, Aino-Maija, additional, Magnussen, Costan G., additional, Sabin, Matthew A., additional, Juonala, Markus, additional, Janner, Marco, additional, Burgner, David P., additional, Schwab, Ursula, additional, Haapala, Eero A., additional, Heitmann, Berit L., additional, Simpson, Stephen J., additional, Raubenheimer, David, additional, and Lakka, Timo A., additional

Published
2023
Full Text
View/download PDF

14. Expanding the p.(Arg85Trp) Variant-Specific Phenotype of HNF4A: Features of Glycogen Storage Disease, Liver Cirrhosis, Impaired Mitochondrial Function, and Glomerular Changes

Author

Grassi, Mara, primary, Laubscher, Bernard, additional, Pandey, Amit V., additional, Tschumi, Sibylle, additional, Graber, Franziska, additional, Schaller, André, additional, Janner, Marco, additional, Aeberli, Daniel, additional, Hewer, Ekkehard, additional, Nuoffer, Jean-Marc, additional, and Gautschi, Matthias, additional

Published
2023
Full Text
View/download PDF

16. Mutation Update of the CLCN5 Gene Responsible for Dent Disease 1

Author

Mansour-Hendili, Lamisse, Blanchard, Anne, Le Pottier, Nelly, Roncelin, Isabelle, Lourdel, Stéphane, Treard, Cyrielle, González, Wendy, Vergara-Jaque, Ariela, Morin, Gilles, Colin, Estelle, Holder-Espinasse, Muriel, Bacchetta, Justine, Baudouin, Véronique, Benoit, Stéphane, Bérard, Etienne, Bourdat-Michel, Guylhène, Bouchireb, Karim, Burtey, Stéphane, Cailliez, Mathilde, Cardon, Gérard, Cartery, Claire, Champion, Gerard, Chauveau, Dominique, Cochat, Pierre, Dahan, Karin, De la Faille, Renaud, Debray, François-Guillaume, Dehoux, Laurenne, Deschenes, Georges, Desport, Estelle, Devuyst, Olivier, Dieguez, Stella, Emma, Francesco, Fischbach, Michel, Fouque, Denis, Fourcade, Jacques, François, Hélène, Gilbert-Dussardier, Brigitte, Hannedouche, Thierry, Houillier, Pascal, Izzedine, Hassan, Janner, Marco, Karras, Alexandre, Knebelmann, Bertrand, Lavocat, Marie-Pierre, Lemoine, Sandrine, Leroy, Valérie, Loirat, Chantal, Macher, Marie-Alice, Martin-Coignard, Dominique, Morin, Denis, Niaudet, Patrick, Nivet, Hubert, Nobili, François, Novo, Robert, Faivre, Laurence, Rigothier, Claire, Roussey-Kesler, Gwenaëlle, Salomon, Remi, Schleich, Andreas, Sellier-Leclerc, Anne-Laure, Soulami, Kenza, Tiple, Aurélien, Ulinski, Tim, Vanhille, Philippe, Van Regemorter, Nicole, Jeunemaître, Xavier, and Vargas-Poussou, Rosa

Published
2015
Full Text
View/download PDF

18. Modeling of levothyroxine in newborns and infants with congenital hypothyroidism: challenges and opportunities of a rare disease multi-center study

Author

Koch, Gilbert; https://orcid.org/0000-0002-9386-0506, Steffens, Britta, Leroux, Stephanie, Gotta, Verena, Schropp, Johannes, Gächter, Pascal, Bachmann, Freya, Welzel, Tatjana, Janner, Marco, L’Allemand, Dagmar, Konrad, Daniel; https://orcid.org/0000-0001-9067-4356, Szinnai, Gabor; https://orcid.org/0000-0003-0559-2597, Pfister, Marc, Koch, Gilbert; https://orcid.org/0000-0002-9386-0506, Steffens, Britta, Leroux, Stephanie, Gotta, Verena, Schropp, Johannes, Gächter, Pascal, Bachmann, Freya, Welzel, Tatjana, Janner, Marco, L’Allemand, Dagmar, Konrad, Daniel; https://orcid.org/0000-0001-9067-4356, Szinnai, Gabor; https://orcid.org/0000-0003-0559-2597, and Pfister, Marc

Abstract

Modeling of retrospectively collected multi-center data of a rare disease in pediatrics is challenging because laboratory data can stem from several decades measured with different assays. Here we present a retrospective pharmacometrics (PMX) based data analysis of the rare disease congenital hypothyroidism (CH) in newborns and infants. Our overall aim is to develop a model that can be applied to optimize dosing in this pediatric patient population since suboptimal treatment of CH during the first 2 years of life is associated with a reduced intelligence quotient between 10 and 14 years. The first goal is to describe a retrospectively collected dataset consisting of 61 newborns and infants with CH up to 2 years of age. Overall, 505 measurements of free thyroxine (FT4) and 510 measurements of thyrotropin or thyroid-stimulating hormone were available from patients receiving substitution treatment with levothyroxine (LT4). The second goal is to introduce a scale/location-scale normalization method to merge available FT4 measurements since 34 different postnatal age- and assay-specific laboratory reference ranges were applied. This method takes into account the change of the distribution of FT4 values over time, i.e. a transformation from right-skewed towards normality during LT4 treatment. The third goal is to develop a practical and useful PMX model for LT4 treatment to characterize FT4 measurements, which is applicable within a clinical setting. In summary, a time-dependent normalization method and a practical PMX model are presented. Since there is no on-going or planned development of new pharmacological approaches for CH, PMX based modeling and simulation can be leveraged to personalize dosing with the goal to enhance longer-term neurological outcome in children with the rare disease CH.

Published
2021

19. Impact of Type 1 Diabetes Mellitus on Bone Health in Children.

Author

Janner, Marco and Saner, Christoph

Subjects
*BONE health, *TYPE 1 diabetes, *DUAL-energy X-ray absorptiometry, *BONE density, *CHILDREN'S health, *INSULIN
Abstract

This paper gives an overview of the impact of type 1 diabetes on bone health in children and adolescents. Firstly, we analyse studies using dual X-ray absorptiometry to assess bone mineral content and bone mineral density. Then, we discuss modern, non-invasive techniques including peripheral quantitative computer tomography (pQCT) and high-resolution pQCT for the detailed assessment of bone health aspects including bone mass, bone geometry, bone microarchitecture, and bone strength. Thereafter, we explore some of the mechanisms that are responsible for diabetic bone disease in children, like low bone turnover and high sclerostin levels. Finally, we summarize some of the evidence for the importance of microvascular disease in the pathophysiology of diabetic bone disease. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

20. Autosomal-Recessive Mutations in MESD Cause Osteogenesis Imperfecta

Author

Moosa, Shahida, Yamamoto, Guilherme L., Garbes, Lutz, Keupp, Katharina, Beleza-Meireles, Ana, Moreno, Carolina Araujo, Valadares, Eugenia Ribeiro, de Sousa, Sérgio B., Maia, Sofia, Saraiva, Jorge, Honjo, Rachel S., Kim, Chong Ae, Cabral de Menezes, Hamilton, Lausch, Ekkehart, Lorini, Pablo Villavicencio, Lamounier, Arsonval, Jr., Carniero, Tulio Canella Bezerra, Giunta, Cecilia, Rohrbach, Marianne, Janner, Marco, Semler, Oliver, Beleggia, Filippo, Li, Yun, Yigit, Gökhan, Reintjes, Nadine, Altmüller, Janine, Nürnberg, Peter, Cavalcanti, Denise P., Zabel, Bernhard, Warman, Matthew L., Bertola, Debora R., Wollnik, Bernd, and Netzer, Christian

Published
2019
Full Text
View/download PDF

25. Androgen production in pediatric adrenocortical tumors may occur via both the classic and/or the alternative backdoor pathway

Author

Marti, Nesa Magdalena, Malikova, Jana, Galván Hernández, José Alberto, Aebischer, Maude, Janner, Marco, Sumnik, Zdenek, Obermannova, Barbora, Escher, Geneviève, Perren, Aurel, and Flück Pandey, Christa Emma

Subjects
570 Life sciences, biology, urologic and male genital diseases, 610 Medicine & health
Abstract

Children with adrenocortical tumors (ACTs) often present with virilization due to high tumoral androgen production, with dihydrotestosterone (DHT) as most potent androgen. Recent work revealed two pathways for DHT biosynthesis, the classic and the backdoor pathway. Usage of alternate routes for DHT production has been reported in castration-resistant prostate cancer, CAH and PCOS. To assess whether the backdoor pathway may contribute to the virilization of pediatric ACTs, we investigated seven children suffering from androgen producing tumors using steroid profiling and immunohistochemical expression studies. All cases produced large amounts of androgens of the classic and/or backdoor pathway. Variable expression of steroid enzymes was observed in carcinomas and adenomas. We found no discriminative pattern. This suggests that enhanced androgen production in pediatric ACTs is the result of deregulated steroidogenesis through multiple steroid pathways. Thus future treatments of ACTs targeting androgen overproduction should consider these novel steroid production pathways.

Published
2017
Full Text
View/download PDF

26. IGHD II: A Novel GH-1 Gene Mutation (GH-L76P) Severely Affects GH Folding, Stability, and Secretion

Author

Miletta, Maria Consolata, Eblé, Andrée, Janner, Marco, Parween, Shaheena, Pandey, Amit Vikram, Flück, Christa Emma, and Mullis, Primus-Eugen

Subjects
610 Medicine & health
Abstract

CONTEXT The autosomal dominant form of GH deficiency (IGHD II) is characterized by markedly reduced GH secretion combined with low concentrations of IGF-1 leading to short stature. OBJECTIVE Structure-function analysis of a missense mutation in the GH-1 gene converting codon 76 from leucine (L) to proline (P) yielding a mutant GH-L76P peptide. DESIGN, SETTINGS, AND PATIENTS Heterozygosity for GH-L76P/wt-GH was identified in a nonconsanguineous Spanish family. The index patients, two siblings, a boy and a girl, were referred for assessment of their short stature (-3.2 and -3.8 SD). Their grandmother, father, and aunt were also carrying the same mutation and showed severe short stature; therefore, IGHD II was diagnosed. INTERVENTIONS AND RESULTS AtT-20 cells coexpressing both wt-GH and GH-L76P showed a reduced GH secretion (P < .001) after forskolin stimulation when compared with the cells expressing only wt-GH. In silico mutagenesis and molecular dynamics simulations presented alterations of correct folding and mutant stability compared with wt-GH. Therefore, further structural analysis of the GH-L76P mutant was performed using expressed and purified proteins in Escherichia coli by thermofluor assay and fast degradation proteolysis assay. Both assays revealed that the GH-L76P mutant is unstable and misfolded compared to wt-GH confirming the bioinformatic model prediction. CONCLUSIONS This is the first report of a family suffering from short stature caused by IGHD II, which severely affects intracellular GH folding and stability as well as secretion, highlighting the necessity of functional analysis of any GH variant for defining new mechanisms as a cause for IGHD II.

Published
2015
Full Text
View/download PDF

29. Mutation Update of theCLCN5Gene Responsible for Dent Disease 1

Author

Mansour-Hendili, Lamisse, primary, Blanchard, Anne, additional, Le Pottier, Nelly, additional, Roncelin, Isabelle, additional, Lourdel, Stéphane, additional, Treard, Cyrielle, additional, González, Wendy, additional, Vergara-Jaque, Ariela, additional, Morin, Gilles, additional, Colin, Estelle, additional, Holder-Espinasse, Muriel, additional, Bacchetta, Justine, additional, Baudouin, Véronique, additional, Benoit, Stéphane, additional, Bérard, Etienne, additional, Bourdat-Michel, Guylhène, additional, Bouchireb, Karim, additional, Burtey, Stéphane, additional, Cailliez, Mathilde, additional, Cardon, Gérard, additional, Cartery, Claire, additional, Champion, Gerard, additional, Chauveau, Dominique, additional, Cochat, Pierre, additional, Dahan, Karin, additional, De la Faille, Renaud, additional, Debray, François-Guillaume, additional, Dehoux, Laurenne, additional, Deschenes, Georges, additional, Desport, Estelle, additional, Devuyst, Olivier, additional, Dieguez, Stella, additional, Emma, Francesco, additional, Fischbach, Michel, additional, Fouque, Denis, additional, Fourcade, Jacques, additional, François, Hélène, additional, Gilbert-Dussardier, Brigitte, additional, Hannedouche, Thierry, additional, Houillier, Pascal, additional, Izzedine, Hassan, additional, Janner, Marco, additional, Karras, Alexandre, additional, Knebelmann, Bertrand, additional, Lavocat, Marie-Pierre, additional, Lemoine, Sandrine, additional, Leroy, Valérie, additional, Loirat, Chantal, additional, Macher, Marie-Alice, additional, Martin-Coignard, Dominique, additional, Morin, Denis, additional, Niaudet, Patrick, additional, Nivet, Hubert, additional, Nobili, François, additional, Novo, Robert, additional, Faivre, Laurence, additional, Rigothier, Claire, additional, Roussey-Kesler, Gwenaëlle, additional, Salomon, Remi, additional, Schleich, Andreas, additional, Sellier-Leclerc, Anne-Laure, additional, Soulami, Kenza, additional, Tiple, Aurélien, additional, Ulinski, Tim, additional, Vanhille, Philippe, additional, Van Regemorter, Nicole, additional, Jeunemaître, Xavier, additional, and Vargas-Poussou, Rosa, additional

Published
2015
Full Text
View/download PDF

32. Mutations in SLC34A3/NPT2c Are Associated with Kidney Stones and Nephrocalcinosis

Author

Dasgupta, Debayan, Wee, Mark J., Reyes, Monica, Li, Yuwen, Simm, Peter J., Sharma, Amita, Schlingmann, Karl-Peter, Janner, Marco, Biggin, Andrew, Lazier, Joanna, Gessner, Michaela, Chrysis, Dionisios, Tuchman, Shamir, Baluarte, H. Jorge, Levine, Michael A., Tiosano, Dov, Insogna, Karl, Hanley, David A., Carpenter, Thomas O., Ichikawa, Shoji, Hoppe, Bernd, Konrad, Martin, Saevendahl, Lars, Munns, Craig F., Lee, Hang, Jueppner, Harald, Bergwitz, Clemens, Dasgupta, Debayan, Wee, Mark J., Reyes, Monica, Li, Yuwen, Simm, Peter J., Sharma, Amita, Schlingmann, Karl-Peter, Janner, Marco, Biggin, Andrew, Lazier, Joanna, Gessner, Michaela, Chrysis, Dionisios, Tuchman, Shamir, Baluarte, H. Jorge, Levine, Michael A., Tiosano, Dov, Insogna, Karl, Hanley, David A., Carpenter, Thomas O., Ichikawa, Shoji, Hoppe, Bernd, Konrad, Martin, Saevendahl, Lars, Munns, Craig F., Lee, Hang, Jueppner, Harald, and Bergwitz, Clemens

Abstract

Compound heterozygous and homozygous (comp/hom) mutations in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium (Na+)-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate wasting resulting in hypophosphatemia, correspondingly elevated 1,25(OH)(2) vitamin D levels, hypercalciuria, and rickets/osteomalacia. Similar, albeit less severe, biochemical changes are observed in heterozygous (het) carriers and indistinguishable from those changes encountered in idiopathic hypercalciuria (IH). Here, we report a review of clinical and laboratory records of 133 individuals from 27 kindreds, including 5 previously unreported HHRH kindreds and two cases with IH, in which known and novel SLC34A3 mutations (c.1357delTTC [p.F453del]; c.G1369A [p.G457S]; c.367delC) were identified. Individuals with mutations affecting both SLC34A3 alleles had a significantly increased risk of kidney stone formation or medullary nephrocalcinosis, namely 46% compared with 6% observed in healthy family members carrying only the wild-type SLC34A3 allele (P=0.005) or 5.64% in the general population (P<0.001). Renal calcifications were also more frequent in het carriers (16%; P=0.003 compared with the general population) and were more likely to occur in comp/hom and het individuals with decreased serum phosphate (odds ratio [OR], 0.75, 95% confidence interval [95% CI], 0.59 to 0.96; P=0.02), decreased tubular reabsorption of phosphate (OR, 0.41; 95% CI, 0.23 to 0.72; P=0.002), and increased serum 1,25(OH)(2) vitamin D (OR, 1.22; 95% CI, 1.05 to 1.41; P=0.008). Additional studies are needed to determine whether these biochemical parameters are independent of genotype and can guide therapy to prevent nephrocalcinosis, nephrolithiasis, and potentially, CKD.

Published
2014

33. Mutations in SLC34A3/NPT2c Are Associated with Kidney Stones and Nephrocalcinosis

Author

Dasgupta, Debayan, primary, Wee, Mark J., additional, Reyes, Monica, additional, Li, Yuwen, additional, Simm, Peter J., additional, Sharma, Amita, additional, Schlingmann, Karl-Peter, additional, Janner, Marco, additional, Biggin, Andrew, additional, Lazier, Joanna, additional, Gessner, Michaela, additional, Chrysis, Dionisios, additional, Tuchman, Shamir, additional, Baluarte, H. Jorge, additional, Levine, Michael A., additional, Tiosano, Dov, additional, Insogna, Karl, additional, Hanley, David A., additional, Carpenter, Thomas O., additional, Ichikawa, Shoji, additional, Hoppe, Bernd, additional, Konrad, Martin, additional, Sävendahl, Lars, additional, Munns, Craig F., additional, Lee, Hang, additional, Jüppner, Harald, additional, and Bergwitz, Clemens, additional

Published
2014
Full Text
View/download PDF

35. Osteogenesis imperfecta: Klinik, Diagnose und Management vom Kindes- bis ins Erwachsenenalter

Author

Bonafe, Luisa, Giunta, Cecilia, Hasler, Carol, Janner, Marco C, Kränzlin, Marius, Link, Bianca, Meier, Christian, Ramseier, Leonhard E, Rohrbach, Marianne, Unger, Sheila, Bonafe, Luisa, Giunta, Cecilia, Hasler, Carol, Janner, Marco C, Kränzlin, Marius, Link, Bianca, Meier, Christian, Ramseier, Leonhard E, Rohrbach, Marianne, and Unger, Sheila

Published
2013

36. El mundo rural de Mágina. Una aproximación ecocrítica a El viento de la Luna de Antonio Muñoz Molina

Author

Janner, Marco, Leuenberger, Daniel, Janner, Marco, and Leuenberger, Daniel

Abstract

In El viento de la Luna (The Wind of the Moon) Antonio Muñoz Molina returns to the imaginary world of Mágina, a place where Nature plays a determinant role. Our ecocritic lecture is focussing on the relation between mankind and environment., En El viento de la Luna Antonio Muñoz Molina regresa al mundo imaginario de Mágina, espacio en el que la Naturaleza desempeña un papel determinante. Nuestra lectura ecocrítica sitúa en un primer plano la relación entre el hombre y el medio ambiente.

Published
2008

44. IGHD II: A Novel GH-1Gene Mutation (GH-L76P) Severely Affects GH Folding, Stability, and Secretion

Author

Miletta, Maria Consolata, Eblé, Andrée, Janner, Marco, Parween, Shaheena, Pandey, Amit V., Flück, Christa E., and Mullis, Primus-E.

Abstract

Context:The autosomal dominant form of GH deficiency (IGHD II) is characterized by markedly reduced GH secretion combined with low concentrations of IGF-1 leading to short stature.Objective:Structure-function analysis of a missense mutation in the GH-1gene converting codon 76 from leucine (L) to proline (P) yielding a mutant GH-L76P peptide.Design, Settings, and Patients:Heterozygosity for GH-L76P/wt-GH was identified in a nonconsanguineous Spanish family. The index patients, two siblings, a boy and a girl, were referred for assessment of their short stature (−3.2 and −3.8 SD). Their grandmother, father, and aunt were also carrying the same mutation and showed severe short stature; therefore, IGHD II was diagnosed.Interventions and Results:AtT-20 cells coexpressing both wt-GH and GH-L76P showed a reduced GH secretion (P< .001) after forskolin stimulation when compared with the cells expressing only wt-GH. In silico mutagenesis and molecular dynamics simulations presented alterations of correct folding and mutant stability compared with wt-GH. Therefore, further structural analysis of the GH-L76P mutant was performed using expressed and purified proteins in Escherichia coliby thermofluor assay and fast degradation proteolysis assay. Both assays revealed that the GH-L76P mutant is unstable and misfolded compared to wt-GH confirming the bioinformatic model prediction.Conclusions:This is the first report of a family suffering from short stature caused by IGHD II, which severely affects intracellular GH folding and stability as well as secretion, highlighting the necessity of functional analysis of any GH variant for defining new mechanisms as a cause for IGHD II.

Published
2015
Full Text
View/download PDF

45. Clinical and biochemical description of a novel CYP21A2gene mutation 962_963insA using a new 3D model for the P450c21 protein

Author

Janner, Marco, Pandey, Amit V, Mullis, Primus E, and Flück, Christa E

Abstract

Objective: A severely virilized 46, XX newborn girl was referred to our center for evaluation and treatment of congenital adrenal hyperplasia (CAH) because of highly elevated 17α-hydroxyprogesterone levels at newborn screening; biochemical tests confirmed the diagnosis of salt-wasting CAH. Genetic analysis revealed that the girl was compound heterozygote for a previously reported Q318X mutation in exon 8 and a novel insertion of an adenine between nucleotides 962 and 963 in exon 4 of the CYP21A2gene. This 962_963insA mutation created a frameshift leading to a stop codon at amino acid 161 of the P450c21 protein.Aim and methods: To better understand structure–function relationships of mutant P450c21 proteins, we performed multiple sequence alignments of P450c21 with three mammalian P450s (P450 2C8, 2C9 and 2B4) with known structures as well as with human P450c17. Comparative molecular modeling of human P450c21 was then performed by MODELLER using the X-ray crystal structure of rabbit P450 2B4 as a template.Results: The new three dimensional model of human P450c21 and the sequence alignment were found to be helpful in predicting the role of various amino acids in P450c21, especially those involved in heme binding and interaction with P450 oxidoreductase, the obligate electron donor.Conclusion: Our model will help in analyzing the genotype–phenotype relationship of P450c21 mutations which have not been tested for their functional activity in an in vitroassay.

Published
2006
Full Text
View/download PDF

46. Mutation Update of the CLCN5 Gene Responsible for Dent Disease 1

Author

Dahan, Karin, Benoit, Stéphane, Dieguez, Stella, Champion, Gerard, Janner, Marco, Treard, Cyrielle, Dehoux, Laurenne, Cartery, Claire, Emma, Francesco, Cardon, Gérard, Ulinski, Tim, Bourdat-Michel, Guylhène, Novo, Robert, Lourdel, Stéphane, Mansour-Hendili, Lamisse, De La Faille, Renaud, Tiple, Aurélien, Devuyst, Olivier, González, Wendy, Hannedouche, Thierry, Bérard, Etienne, Holder-Espinasse, Muriel, Morin, Gilles, Vargas-Poussou, Rosa, Macher, Marie-Alice, Fischbach, Michel, Sellier-Leclerc, Anne-Laure, François, Hélène, Loirat, Chantal, Deschenes, Georges, Van Regemorter, Nicole, Nobili, François, Morin, Denis, Schleich, Andreas, Niaudet, Patrick, Roussey-Kesler, Gwenaëlle, Blanchard, Anne, Bacchetta, Justine, Vergara-Jaque, Ariela, Chauveau, Dominique, Martin-Coignard, Dominique, Leroy, Valérie, Faivre, Laurence, Izzedine, Hassan, Cochat, Pierre, Fouque, Denis, Soulami, Kenza, Lavocat, Marie-Pierre, Knebelmann, Bertrand, Lemoine, Sandrine, Nivet, Hubert, Jeunemaître, Xavier, Karras, Alexandre, Cailliez, Mathilde, Gilbert-Dussardier, Brigitte, Le Pottier, Nelly, Baudouin, Véronique, Fourcade, Jacques, Debray, François-Guillaume, Desport, Estelle, Roncelin, Isabelle, Rigothier, Claire, Bouchireb, Karim, Vanhille, Philippe, Colin, Estelle, Salomon, Remi, Burtey, Stéphane, and Houillier, Pascal

Subjects
610 Medicine & health, 3. Good health
Abstract

Dent disease is a rare X-linked tubulopathy characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis and/or nephrolithiasis, progressive renal failure, and variable manifestations of other proximal tubule dysfunctions. It often progresses over a few decades to chronic renal insufficiency, and therefore molecular characterization is important to allow appropriate genetic counseling. Two genetic subtypes have been described to date: Dent disease 1 is caused by mutations of the CLCN5 gene, coding for the chloride/proton exchanger ClC-5; and Dent disease 2 by mutations of the OCRL gene, coding for the inositol polyphosphate 5-phosphatase OCRL-1. Herein, we review previously reported mutations (n = 192) and their associated phenotype in 377 male patients with Dent disease 1 and describe phenotype and novel (n = 42) and recurrent mutations (n = 24) in a large cohort of 117 Dent disease 1 patients belonging to 90 families. The novel missense and in-frame mutations described were mapped onto a three-dimensional homology model of the ClC-5 protein. This analysis suggests that these mutations affect the dimerization process, helix stability, or transport. The phenotype of our cohort patients supports and extends the phenotype that has been reported in smaller studies.

47. Broad range of phenotypes in an international cohort of 75 DSD individuals with SF-1/NR5A1 variants

Author

Kouri, Chrysanthi, Sommer, Grit, Ahmed, Faisal, Balsamo, Antonio, Baronio, Federico, Bryce, Jillian, Camats, Nuria, Cetinkaya, Semra, Hedi L. Claahsen - van der Grinten, Cools, Martine, Darendeliler, Fatma Feyza, Davies, Justin H., Fabbri-Scallet, Helena, Globa, Evgenia, Guerra-Junior, Gil, Guran, Tulay, Hannema, Sabine, Hiort, Olaf, Janner, Marco, Kalinchenko, Natalia, Lachlan, Katherine, Kolesinska, Zofia, L Allemand, Dagmar, Lang-Muritano, Mariarosaria, Lucas-Herald, Angela, Lapiscina Martin, Idoia Martinez, Mazen, Inas, Moenig, Isabel, Muhrer, Julia, Niedziela, Marek, Nordenstrom, Anna, Orman, Burce, Poyrazoglu, Sukran, Tack, Lloyd, Tadokoro-Cuccaro, Rieko, Wasniewska, Malgorzata, Yavas, Zehra, Zelinska, Nataliya, Fluck, Christa E., Pediatrics, Amsterdam Gastroenterology Endocrinology Metabolism, and Amsterdam Reproduction & Development

48. IGHD II: A Novel GH-1 Gene Mutation (GH-L76P) Severely Affects GH Folding, Stability, and Secretion.

Author

Miletta MC, Eblé A, Janner M, Parween S, Pandey AV, Flück CE, and Mullis PE

Subjects
Amino Acid Substitution genetics, Animals, Body Height genetics, Child, Child, Preschool, Codon genetics, Colforsin pharmacology, Computational Biology, Family, Female, Heterozygote, Human Growth Hormone genetics, Human Growth Hormone metabolism, Humans, Infant, Infant, Newborn, Male, Mice, Mutation, Missense genetics, Pedigree, Pregnancy, Protein Conformation, Human Growth Hormone deficiency, Protein Folding
Abstract

Context: The autosomal dominant form of GH deficiency (IGHD II) is characterized by markedly reduced GH secretion combined with low concentrations of IGF-1 leading to short stature., Objective: Structure-function analysis of a missense mutation in the GH-1 gene converting codon 76 from leucine (L) to proline (P) yielding a mutant GH-L76P peptide., Design, Settings, and Patients: Heterozygosity for GH-L76P/wt-GH was identified in a nonconsanguineous Spanish family. The index patients, two siblings, a boy and a girl, were referred for assessment of their short stature (-3.2 and -3.8 SD). Their grandmother, father, and aunt were also carrying the same mutation and showed severe short stature; therefore, IGHD II was diagnosed., Interventions and Results: AtT-20 cells coexpressing both wt-GH and GH-L76P showed a reduced GH secretion (P < .001) after forskolin stimulation when compared with the cells expressing only wt-GH. In silico mutagenesis and molecular dynamics simulations presented alterations of correct folding and mutant stability compared with wt-GH. Therefore, further structural analysis of the GH-L76P mutant was performed using expressed and purified proteins in Escherichia coli by thermofluor assay and fast degradation proteolysis assay. Both assays revealed that the GH-L76P mutant is unstable and misfolded compared to wt-GH confirming the bioinformatic model prediction., Conclusions: This is the first report of a family suffering from short stature caused by IGHD II, which severely affects intracellular GH folding and stability as well as secretion, highlighting the necessity of functional analysis of any GH variant for defining new mechanisms as a cause for IGHD II.

Published
2015
Full Text
View/download PDF

49. High prevalence of vitamin D deficiency in children and adolescents with type 1 diabetes.

Author

Janner M, Ballinari P, Mullis PE, and Flück CE

Subjects
Adolescent, Alkaline Phosphatase blood, Bone Density physiology, Calcium blood, Child, Comorbidity, Cross-Sectional Studies, Diabetes Mellitus, Type 1 blood, Female, Fractures, Spontaneous blood, Fractures, Spontaneous epidemiology, Humans, Male, Parathyroid Hormone blood, Phosphates blood, Prospective Studies, Reference Values, Risk Factors, Switzerland, Vitamin D analogs & derivatives, Vitamin D blood, Vitamin D Deficiency blood, Diabetes Mellitus, Type 1 epidemiology, Vitamin D Deficiency epidemiology
Abstract

Background: Vitamin D is important for bone health. An inadequate supply of vitamin D to the body is associated with a higher fracture risk in the elderly. Young adults with type 1 diabetes are reported to have a lower peak bone mass than healthy individuals, which could possibly lead to an increased fracture risk in the future. The prevalence of vitamin D deficiency in healthy young people is high. Thus, optimal supply of vitamin D may be of particular importance for bone health in children with type 1 diabetes., Methods: In this prospective cross-sectional study we measured serum 25-hydroxy-vitamin D, iPTH, total and ionised calcium, phosphate, and alkaline phosphatase in 129 Swiss children and adolescents with type 1 diabetes., Results: Of the 129 subjects 78 (60.5%) were vitamin D deficient, defined as a 25-hydroxy-vitamin-D level below 50 nmol/L. During the winter this number rose to 84.1%. 25-hydroxy-vitamin-D levels showed marked seasonal fluctuations, whereas there was no correlation with diabetes control. Despite the high prevalence of vitamin D deficiency, we found a low prevalence of secondary hyperparathyroidism in vitamin D deficient diabetic children and adolescents., Conclusions: Prevalence of vitamin D deficiency in diabetic children and adolescents is high. Therefore, screening for vitamin D deficiency and supplementation in children with low vitamin D levels may be considered.

Published
2010
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results