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Your search keyword '"Gil-Pena, H."' showing total 4 results
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4 results on '"Gil-Pena, H."'

1. Novel mutations associated with inherited human calcium-sensing receptor disorders: A clinical genetic study

Author

Gaztambide, S, Ramirez, J, Gomez, M, Montalban, C, Ruiz, R, Socias, C, Boronat, M, Aparicio, C, Bilbao, I, Conde, S, Garcia-Cuartero, B, Jimenez, B, Rodriguez, P, Perez, E, Hidalgo-Barquero, E, Barrio, R, Gonzalez, C, Cordo, C, Cruz, J, Hernandez, J, Fernandez-Ramos, C, Marti, J, Clemente, M, Garcia, L, Rica, I, Martinez, R, Urrutia, I, de LaPiscina, I, Santos, F, Gil-Pena, H, Coto, E, Loredo, V, Ordonez, F, Rodriguez, J, Riera, E, Hernandez, O, Fuente, R, Claramunt, D, Nieto, V, Martin, F, Acosta, H, Trujillo, E, Yanes, M, Lanus, E, Castano, L, Madariaga, L, de Nanclares, G, Garcia-Castano, A, Aguirre, M, Herrero, M, Aguayo, A, Ariceta, G, Meseguer, A, Spanish Endocrinology Grp, and Renal Tube Grp

Abstract

Objective: Molecular diagnosis is a useful diagnostic tool in calcium metabolism disorders. The calcium-sensing receptor (CaSR) is known to play a central role in the regulation of extracellular calcium homeostasis. We performed clinical, biochemical and genetic characterization of sequence anomalies in this receptor in a cohort of 130 individuals from 82 families with suspected alterations in the CASR gene, one of the largest series described. Methods: The CASR gene was screened for mutations by polymerase chain reaction followed by direct Sanger sequencing. Results: Presumed CaSR-inactivating mutations were found in 65 patients from 26 families. These patients had hypercalcemia (median: 11.3 mg/dL) but normal or abnormally high parathyroid hormone (PTH) levels (median: 52 pg/ mL). On the other hand, presumed CaSR-activating mutations were detected in 17 patients from eight families. These patients had a median serum calcium level of 7.4 mg/dL and hypoparathyroidism (median: PTH 13 pg/mL). Further, common polymorphisms previously associated with high blood ionized calcium levels were found in 27 patients (median calcium: 10.6 mg/dL; median PTH: 65 pg/mL) with no other alterations in CASR. Overall, we found 30 different mutations, of which, 14 have not been previously reported (p.Ala26Ser, p.Cys60Arg, plys119lle, p.Leu123Met, p.Glu133Val, p.Gly222Glu, p.Phe351lle, p.Cys542Tyr, p.Cys546Gly, p.Cys677Tyr, p.lle816Val, p.Ala887Asp, p.Glu934*, p.Pro935_Gln945dup). Conclusions: Patients with CASR mutations may not fit the classic clinical pictures of hypercalcemia with hypocalciuria or hypocalcemia with hypercalciuria. Molecular studies are important for confirming the diagnosis and distinguishing it from other entities. Our genetic analysis confirmed CaSR disorders in 82 patients in the study cohort.

Published
2019

2. Treatment and long-term outcome in primary distal renal tubular acidosis

Author

Lopez-Garcia, S.C., Emma, F., Walsh, S.B., Fila, M., Hooman, N., Zaniew, M., Bertholet-Thomas, A., Colussi, G., Burgmaier, K., Levtchenko, E.N., Sharma, J., Singhal, J., Soliman, N.A., Ariceta, G., Basu, B., Murer, L., Tasic, V., Tsygin, A., Decramer, S., Gil-Pena, H., Koster-Kamphuis, L., La Scola, C., Gellermann, J., Konrad, M., Lilien, M., Francisco, T., Tramma, D., Trnka, P., Yuksel, S., Caruso, M.R., Chromek, M., Ekinci, Z., Gambaro, G., Kari, J.A., Konig, J., Taroni, F., Thumfart, J., Trepiccione, F., Winding, L., Wuhl, E., Agbas, A., Belkevich, A., Vargas-Poussou, R., Blanchard, A., Conti, G., Boyer, O., Dursun, I., Pinarbasi, A.S., Melek, E., Miglinas, M., Novo, R., Mallett, A., Milosevic, D., Szczepanska, M., Wente, S., Cheong, H.I., Sinha, R., Gucev, Z., Dufek, S., Iancu, D., Kleta, R., Schaefer, F., Bockenhauer, D., Lopez-Garcia, S.C., Emma, F., Walsh, S.B., Fila, M., Hooman, N., Zaniew, M., Bertholet-Thomas, A., Colussi, G., Burgmaier, K., Levtchenko, E.N., Sharma, J., Singhal, J., Soliman, N.A., Ariceta, G., Basu, B., Murer, L., Tasic, V., Tsygin, A., Decramer, S., Gil-Pena, H., Koster-Kamphuis, L., La Scola, C., Gellermann, J., Konrad, M., Lilien, M., Francisco, T., Tramma, D., Trnka, P., Yuksel, S., Caruso, M.R., Chromek, M., Ekinci, Z., Gambaro, G., Kari, J.A., Konig, J., Taroni, F., Thumfart, J., Trepiccione, F., Winding, L., Wuhl, E., Agbas, A., Belkevich, A., Vargas-Poussou, R., Blanchard, A., Conti, G., Boyer, O., Dursun, I., Pinarbasi, A.S., Melek, E., Miglinas, M., Novo, R., Mallett, A., Milosevic, D., Szczepanska, M., Wente, S., Cheong, H.I., Sinha, R., Gucev, Z., Dufek, S., Iancu, D., Kleta, R., Schaefer, F., and Bockenhauer, D.

Abstract

Contains fulltext : 204259.pdf (publisher's version ) (Closed access), BACKGROUND: Primary distal renal tubular acidosis (dRTA) is a rare disorder, and we aimed to gather data on treatment and long-term outcome. METHODS: We contacted paediatric and adult nephrologists through European professional organizations. Responding clinicians entered demographic, biochemical, genetic and clinical data in an online form. RESULTS: Adequate data were collected on 340 patients (29 countries, female 52%). Mutation testing had been performed on 206 patients (61%); pathogenic mutations were identified in 170 patients (83%). The median (range) presentation age was 0.5 (0-54) years and age at last follow-up was 11.0 (0-70.0) years. Adult height was slightly below average with a mean (SD score) of -0.57 (+/-1.16). There was an increased prevalence of chronic kidney disease (CKD) Stage >/=2 in children (35%) and adults (82%). Nephrocalcinosis was reported in 88%. Nephrolithiasis was more common with SLC4A1 mutations (42% versus 21%). Thirty-six percent had hearing loss, particularly in ATP6V1B1 (88%). The median (interquartile range) prescribed dose of alkali (mEq/kg/day) was 1.9 (1.2-3.3). Adequate metabolic control (normal plasma bicarbonate and normocalciuria) was achieved in 158 patients (51%), more commonly in countries with higher gross domestic product (67% versus 23%), and was associated with higher height and estimated glomerular filtration rate. CONCLUSION: Long-term follow-up from this large dRTA cohort shows an overall favourable outcome with normal adult height for most and no patient with CKD Stage 5. However, 82% of adult patients have CKD Stages 2-4. Importance of adequate metabolic control was highlighted by better growth and renal function but was achieved in only half of patients.

Published
2019

3. Genetic Variation in the H19-IGF2 Cluster Might Confer Risk of Developing Impaired Renal Function

Author

Coto E, Corte C, Tranche S, Gomez J, Reguero J, Alonso B, Iglesias S, Gil-Pena H, Yin X, and Coto-Segura P

Subjects
genetic association, H19, impaired renal function, IGF2, type 2 diabetes, imprinting
Abstract

The H19-IGF2 imprinted gene region could be implicated in the risk of developing impaired renal function (IRF). Our aim was to determine the association of several common H19-IGF2 variants and IRF in a cohort of elderly healthy individuals. The study involved 675 individuals >65 years of age, 184 with type 2 diabetes mellitus (T2DM), and 105 with IRF (estimated glomerular filtration rate [eGFR]

Published
2018

4. Effects of IFIH1 rs1990760 variants on systemic inflammation and outcome in critically ill COVID-19 patients in an observational translational study.

Author

Amado-Rodríguez L, Salgado Del Riego E, Gomez de Ona J, López Alonso I, Gil-Pena H, López-Martínez C, Martín-Vicente P, Lopez-Vazquez A, Gonzalez Lopez A, Cuesta-Llavona E, Rodriguez-Garcia R, Boga JA, Elena Alvarez-Arguelles M, Mayordomo-Colunga J, Vidal-Castineira JR, Crespo I, Fernandez M, Criado L, Salvadores V, Jimeno-Demuth FJ, Blanch L, Prieto B, Fernandez-Fernandez A, Lopez-Larrea C, Coto E, and Albaiceta GM

Subjects
Aged, COVID-19 complications, Critical Illness, DEAD-box RNA Helicases metabolism, Female, Humans, Inflammation metabolism, Male, Middle Aged, COVID-19 genetics, Inflammation genetics, Interferon-Induced Helicase, IFIH1 genetics, SARS-CoV-2 pathogenicity
Abstract

Background: Variants in IFIH1 , a gene coding the cytoplasmatic RNA sensor MDA5, regulate the response to viral infections. We hypothesized that IFIH1 rs199076 variants would modulate host response and outcome after severe COVID-19., Methods: Patients admitted to an intensive care unit (ICU) with confirmed COVID-19 were prospectively studied and rs1990760 variants determined. Peripheral blood gene expression, cell populations, and immune mediators were measured. Peripheral blood mononuclear cells from healthy volunteers were exposed to an MDA5 agonist and dexamethasone ex-vivo, and changes in gene expression assessed. ICU discharge and hospital death were modeled using rs1990760 variants and dexamethasone as factors in this cohort and in-silico clinical trials., Results: About 227 patients were studied. Patients with the IFIH1 rs1990760 TT variant showed a lower expression of inflammation-related pathways, an anti-inflammatory cell profile, and lower concentrations of pro-inflammatory mediators. Cells with TT variant exposed to an MDA5 agonist showed an increase in IL6 expression after dexamethasone treatment. All patients with the TT variant not treated with steroids survived their ICU stay (hazard ratio [HR]: 2.49, 95% confidence interval [CI]: 1.29-4.79). Patients with a TT variant treated with dexamethasone showed an increased hospital mortality (HR: 2.19, 95% CI: 1.01-4.87) and serum IL-6. In-silico clinical trials supported these findings., Conclusions: COVID-19 patients with the IFIH1 rs1990760 TT variant show an attenuated inflammatory response and better outcomes. Dexamethasone may reverse this anti-inflammatory phenotype., Funding: Centro de Investigación Biomédica en Red (CB17/06/00021), Instituto de Salud Carlos III (PI19/00184 and PI20/01360), and Fundació La Marató de TV3 (413/C/2021)., Competing Interests: LA, ES, JG, IL, HG, CL, PM, AL, AG, EC, RR, JB, ME, JM, JV, IC, MF, LC, VS, FJ, LB, BP, AF, CL, EC, GA No competing interests declared, (© 2022, Amado-Rodríguez et al.)

Published
2022
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