29 results on '"Miglietti, N"'
Search Results
2. Cluster Analysis Identifies Distinct Pathogenetic Patterns in C3 Glomerulopathies/Immune Complex–Mediated Membranoproliferative GN
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Iatropoulos, Paraskevas, Daina, Erica, Curreri, Manuela, Piras, Rossella, Valoti, Elisabetta, Mele, Caterina, Bresin, Elena, Gamba, Sara, Alberti, Marta, Breno, Matteo, Perna, Annalisa, Bettoni, Serena, Sabadini, Ettore, Murer, Luisa, Vivarelli, Marina, Noris, Marina, Remuzzi, Giuseppe, Bottanelli, L., Donadelli, R., Cuccarolo, P., Abbate, M., Carrara, C., Cannata, A., Ferrari, S., Gaspari, F., Stucchi, N., Bassani, C., Lena, M., Omati, G., Taruscia, D., Bellantuono, R., Giordano, M., Messina, G., Caruso, M., Gotti, E., Mescia, F., Perticucci, E., Schieppati, A., Verdoni, L., Berto, M., Baraldi, O., Montini, G., Pasini, A., Passler, W., Degasperi, T., Gaggiotti, M., Gregorini, G., Miglietti, N., Guarnieri, A., Cirami, L., Roperto, R. M., Di Giorgio, G., Barbano, G., Innocenti, M. L. D., Ghiggeri, G. M., Magnasco, A., Rolla, D., Casartelli, D., Lambertini, D., Maggio, M., Cosci, P. M., Conti, G., Amar, K., Ardissino, G., Marinosci, A., Sinico, R. A., Montoli, A., Bonucchi, D., Facchini, F., Furci, L., Ferretti, A., Nuzzi, F., Pecoraro, C., Visciano, B., Canavese, C., Radin, E., Stratta, P., Nordio, M., Benetti, E., Parolin, M., Alberici, F., Manenti, L., Brugnano, R., Manenti, F., Capitanini, A., Emma, F., Massella, L., Rosa, M., Mazzon, M., Basso, E., Besso, L., Lavacca, A., Mella, A., Bertero, M., Coppo, R., Peruzzi, L., Porcellini, M. G., Piccoli, G. B., Clari, R., Pasi, A., Gangemi, C., Alfandary, H., Dagan, A., Conceiçao, M., Sameiro, F. M., Croze, L., Malvezzi, P., Tsygin, A., Zelan, B., Nastasi, null, Iatropoulos, P, Daina, E, Curreri, M, Piras, R, Valoti, E, Mele, C, Bresin, E, Gamba, S, Alberti, M, Breno, M, Perna, A, Bettoni, S, Sabadini, E, Murer, L, Vivarelli, M, Noris, M, Remuzzi, G, Bottanelli, L, Donadelli, R, Cuccarolo, P, Abbate, M, Carrara, C, Cannata, A, Ferrari, S, Gaspari, F, Stucchi, N, Bassani, C, Lena, M, Omati, G, Taruscia, D, Bellantuono, R, Giordano, M, Messina, G, Caruso, M, Gotti, E, Mescia, F, Perticucci, E, Schieppati, A, Verdoni, L, Berto, M, Baraldi, O, Montini, G, Pasini, A, Passler, W, Degasperi, T, Gaggiotti, M, Gregorini, G, Miglietti, N, Guarnieri, A, Cirami, L, Roperto, R, Di Giorgio, G, Barbano, G, Innocenti, M, Ghiggeri, G, Magnasco, A, Rolla, D, Casartelli, D, Lambertini, D, Maggio, M, Cosci, P, Conti, G, Amar, K, Ardissino, G, Marinosci, A, Sinico, R, Montoli, A, Bonucchi, D, Facchini, F, Furci, L, Ferretti, A, Nuzzi, F, Pecoraro, C, Visciano, B, Canavese, C, Radin, E, Stratta, P, Nordio, M, Benetti, E, Parolin, M, Alberici, F, Manenti, L, Brugnano, R, Manenti, F, Capitanini, A, Emma, F, Massella, L, Rosa, M, Mazzon, M, Basso, E, Besso, L, Lavacca, A, Mella, A, Bertero, M, Coppo, R, Peruzzi, L, Porcellini, M, Piccoli, G, Clari, R, Pasi, A, Gangemi, C, Alfandary, H, Dagan, A, Conceiçao, M, Sameiro, F, Croze, L, Malvezzi, P, Tsygin, A, Zelan, B, and Nastasi, N
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0301 basic medicine ,Complement system ,Glomerulonephritis, Membranoproliferative ,membranoproliferative glomerulonephritis (MPGN) ,030232 urology & nephrology ,Disease ,Antigen-Antibody Complex ,Biology ,Kidney ,03 medical and health sciences ,0302 clinical medicine ,Glomerulopathy ,Clinical Research ,medicine ,Dense Deposit Disease ,Humans ,C3 glomerulopathy ,General Medicine ,Complement System Proteins ,C3 glomerulonephriti ,medicine.disease ,C3-convertase ,Immune complex ,030104 developmental biology ,Nephrology ,Immunology ,Alternative complement pathway ,Nephrotic syndrome ,Rare disease - Abstract
Membranoproliferative GN (MPGN) was recently reclassified as alternative pathway complement–mediated C3 glomerulopathy (C3G) and immune complex–mediated membranoproliferative GN (IC-MPGN). However, genetic and acquired alternative pathway abnormalities are also observed in IC-MPGN. Here, we explored the presence of distinct disease entities characterized by specific pathophysiologic mechanisms. We performed unsupervised hierarchical clustering, a data-driven statistical approach, on histologic, genetic, and clinical data and data regarding serum/plasma complement parameters from 173 patients with C3G/IC-MPGN. This approach divided patients into four clusters, indicating the existence of four different pathogenetic patterns. Specifically, this analysis separated patients with fluid-phase complement activation (clusters 1–3) who had low serum C3 levels and a high prevalence of genetic and acquired alternative pathway abnormalities from patients with solid-phase complement activation (cluster 4) who had normal or mildly altered serum C3, late disease onset, and poor renal survival. In patients with fluid-phase complement activation, those in clusters 1 and 2 had massive activation of the alternative pathway, including activation of the terminal pathway, and the highest prevalence of subendothelial deposits, but those in cluster 2 had additional activation of the classic pathway and the highest prevalence of nephrotic syndrome at disease onset. Patients in cluster 3 had prevalent activation of C3 convertase and highly electron-dense intramembranous deposits. In addition, we provide a simple algorithm to assign patients with C3G/IC-MPGN to specific clusters. These distinct clusters may facilitate clarification of disease etiology, improve risk assessment for ESRD, and pave the way for personalized treatment.
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- 2017
3. Juvenile Nephronophthisis and Related Variants: Clinical Features and Molecular Approach
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Caridi, G., primary, Dagnino, M., additional, Miglietti, N., additional, Carrea, A., additional, Perfumo, F., additional, Gusmano, R., additional, and Ghiggeri, G.M., additional
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- 2001
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4. Shiga Toxin–Producing Escherichia coli Infections Associated with Hemolytic Uremic Syndrome, Italy, 1988–2000
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Tozzi, A. E., Caprioli, A., Minelli, F., Gianviti, A., Petris, L., Edefonti, A., Giovanni Montini, Ferretti, A., Palo, T., Gaido, M., Rizzoni, G., Bettinelli, A., Capasso, G., Caringella, A., Coppo, R., Lama, G., Li Volti, S., Maffei, S., Maringhini, S., Miglietti, N., Pecoraro, C., Pela, I., Pennesi, M., Penza, R., Peratoner, L., Perfumo, F., Ratsche, I., Salvaggio, E., Setzu, C., Zacchello, G., Tozzi, Ae, Caprioli, A, Minelli, F, Gianviti, A, De Petris, L, Edefonti, A, Montini, G, Ferretti, A, De Palo, T, Gaido, M, Rizzoni, G, A., Bettinelli, Capasso, Giovambattista, Caringella, A, Coppo, R, Lama, G, Li Volti, S, Maffei, S, Maringhini, S, Miglietti, N, Pecoraro, C, Pela, I, Pennesi, M, Penza, R, Peratoner, L, Perfumo, F, Ratsche, I, Salvaggio, E, Setzu, C, and Zacchello, G.
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Microbiology (medical) ,Serotype ,Adolescent ,Population ,lcsh:Medicine ,Escherichia coli O157 ,medicine.disease_cause ,Annual incidence ,Shiga Toxin ,Microbiology ,lcsh:Infectious and parasitic diseases ,fluids and secretions ,Shiga toxin-producing Escherichia coli ,Escherichia coli ,Humans ,Medicine ,HUS ,lcsh:RC109-216 ,Serotyping ,education ,Escherichia coli Infections ,laboratory diagnosis ,education.field_of_study ,biology ,business.industry ,Research ,Incidence ,Incidence (epidemiology) ,lcsh:R ,Shiga toxin ,Virology ,STEC ,Infectious Diseases ,Italy ,Child, Preschool ,Population Surveillance ,Hemolytic-Uremic Syndrome ,biology.protein ,hemolytic uremic syndrome ,bacteria ,epidemiology ,business - Abstract
The mean annual incidence of hemolytic uremic syndrome in persons
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- 2003
5. Human metapneumovirus infection in young children hospitalized with acute respiratory tract disease: virological and clinical features
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Caracciolo, S, Minini, C, Colombrita, D, Rossi, D, Miglietti, N, Vettore, E, Caruso, Arnaldo, and Fiorentini, Simona
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- 2008
6. Unbiased next generation sequencing analysis confirms the existence of autosomal dominant Alport syndrome in a relevant fraction of cases
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Fallerini, C., primary, Dosa, L., additional, Tita, R., additional, Del Prete, D., additional, Feriozzi, S., additional, Gai, G., additional, Clementi, M., additional, La Manna, A., additional, Miglietti, N., additional, Mancini, R., additional, Mandrile, G., additional, Ghiggeri, G.M., additional, Piaggio, G., additional, Brancati, F., additional, Diano, L., additional, Frate, E., additional, Pinciaroli, A.R., additional, Giani, M., additional, Castorina, P., additional, Bresin, E., additional, Giachino, D., additional, De Marchi, M., additional, Mari, F., additional, Bruttini, M., additional, Renieri, A., additional, and Ariani, F., additional
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- 2013
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7. Sindrome di Alport associata a leiomiomatosi diffusa: una sindrome da geni contigui
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Viola, Bf, Scolari, Francesco, Miglietti, N., Tardanico, R., Baronchelli, C., Grazioli, L., and Maiorca, Rosario
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- 2000
8. Sindrome iponatriemica da inappropriata secrezione di ADH (SIADH). Inusuale coinvolgimento cerebrale in paziente con LES e anticorpi anticardiolipina
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Scolari, Francesco, Savoldi, S, Gaggiotti, M, Franceschini, F, Miglietti, N, and Maiorca, Rosario
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- 1992
9. Syndrome of inappropriate Antidiuretic Hormone Secretion (SIADH): an unusual clinical manifestation of cerebral involvement in a patient with LES and Anticardiolipin Antibodies (ACA)
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Scolari, Francesco, Savoldi, S., Gaggiotti, M., Franceschini, R., Miglietti, N., and Maiorca, Rosario
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- 1992
10. Infezioni delle vie urinarie e reflusso vescico-ureterale: rivalutazione dell'approccio diagnostico in una casistica di 210 bambini
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Miglietti, N., Scolari, Francesco, Cavalli, G., and Brunori, A.
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- 1992
11. UTILIZZO DI PROCALCITONINA NELLA DIAGNOSI DELLE POLMONITI ACQUISITE IN COMUNITÀ IN ETÀ PEDIATRICA
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Colombrita, D., primary, Foresti, I., additional, Draghin, E., additional, Caruso, A., additional, Timpano, S., additional, Lombardi, A., additional, and Miglietti, N., additional
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- 2005
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12. Locus heterogeneity of Dent's disease: OCRL1 and TMEM27 genes in patients with no CLCN5 mutations.
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Tosetto E, Addis M, Caridi G, Meloni C, Emma F, Vergine G, Stringini G, Papalia T, Barbano G, Ghiggeri G, Ruggeri L, Miglietti N, D'Angelo A, Melis M, and Anglani F
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- 2009
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13. Juvenile Nephronophthisis and Related Variants: Clinical Features and Molecular Approach.
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Caridi, G., Dagnino, M., Miglietti, N., Carrea, A., Perfumo, F., Gusmano, R., and Ghiggeri, G.M.
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- 2001
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14. Identification of fifteen novel mutations in the SLC12A3 gene encoding the Na-Cl Co-transporter in Italian patients with Gitelman syndrome
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Syrén, M. L., Tedeschi, S., Cesareo, L., Bellantuono, R., Colussi, G., Procaccio, M., Alì, A., Domenici, R., Malberti, F., Sprocati, M., Sacco, M., Miglietti, N., Edefonti, A., Sereni, F., Giorgio CASARI, Coviello, D. A., Bettinelli, A., Syrén, Ml, Tedeschi, S, Cesareo, L, Bellantuono, R, Colussi, G, Procaccio, M, Alì, A, Domenici, R, Malberti, F, Sprocati, M, Sacco, M, Miglietti, N, Edefonti, A, Sereni, F, Casari, GIORGIO NEVIO, Coviello, Da, and Bettinelli, A.
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Symporters ,Receptors, Drug ,Mutation, Missense ,Alkalosis ,Hypokalemia ,DNA ,Sequence Analysis, DNA ,Syndrome ,Sodium Chloride Symporters ,Italy ,Mutation ,Humans ,Calcium ,Magnesium ,Solute Carrier Family 12, Member 3 ,Carrier Proteins ,Polymorphism, Single-Stranded Conformational ,Sequence Deletion - Abstract
The SLC12A3 gene encodes the thiazide-sensitive Na-Cl co-transporter (NCCT) expressed in the apical membrane of the distal convoluted tubule of the kidney. Inactivating mutations of this gene are responsible for Gitelman syndrome (GS), a disorder inherited as an autosomal recessive trait. We searched for SLC12A3 gene mutations in 21 Italian patients with the clinical and biochemical features of GS (hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria, and the absence of nephrocalcinosis). All coding regions with their intron-exon boundaries were analyzed using PCR and SSCP techniques followed by sequencing analysis. We identified 21 different mutations evenly distributed throughout the gene without any mutation hot-spot. Fifteen are novel variants, including 12 missense mutations, one deletion, one deletion-insertion and one splice site mutation: R158Q, T163M, W172R, G316V, G374V, G463E, A464T, S615W, V677M, R852S, R958G, C985Y, 2114-2120delACCAAGT, 2144-2158delGCCTTCTACTCGGATinsTG, and 531-2A>G.
15. Erratum: Identification of fifteen novel mutations in the SLC12A3 gene encoding the Na-Cl co-transporter in Italian patients with Gitelman syndrome (Human mutation (2002) 20:78))
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Syrén, M. -L, Tedeschi, S., Cesareo, L., Bellantuono, R., Colussi, G., Procaccio, M., Alì, A., Domenici, R., Malberti, F., Sprocati, M., Sacco, M., Miglietti, N., Edefonti, A., Sereni, F., Casari, G., Domenico Coviello, and Bettinelli, A.
16. Juvenile nephronophthisis and related variants: Clinical features and molecular approach
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Caridi, G., Dagnino, M., Miglietti, N., Carrea, A., Perfumo, F., Gusmano, R., and Gian Marco Ghiggeri
17. Clinical and auxological evaluation in patients with molecular diagnosis of X-linked nephrogenic diabetes insipidus,Valutazione clinica ed auxolcgica in pazienti con diagnosi molecolare di diabete insipido nefrogenico ad ereditarietà legata al cromosoma X
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Procaccio, M., Bice Chini, Albertazzi, E., Faranda, S., Frattini, A., Vezzoni, P., Fossali, E., Appiani, A. C., Natale, B. D. I., Lukesich, M., Volti, S. L. I., Rosini, A., Einaudi, S., Pecoraro, C., Miglietti, N., Razzoli, E., Maggi, M., and Bettinelli, A.
18. Italian pediatric nutrition survey
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Michelangelo Barbaglia, Luigi Marmetucci, Nicoletta Cimadore, Alessandro Monaci, P. Fiore, Sergio Amarri, Elena Brunori, Maddalena Cioni, Carla Russo, Monica Barrani, P. Gandullia, Giovanna Zuin, Giuseppe Parisi, Rita Bellomo Anna, Michele Pinon, Nunzia Miglietti, Francesca Lizzoli, Elisa Mazzoni, Giulia Bardasi, Marisa Zoppo, Giacomo Cagnoli, S. Borodani, L. Forchielli, Monica Tulli, Fina Belli, Michele Salata, Giovanna Verlato, Vittoria Opinto, Roberto Bonaudo, Luisella Angelotti, Giulia Bruni, Elena Uga, Costantino De Giacomo, Antonietta Antonini Monica, Riccardo Guanà, Flavia Urbano, Rosaria Abate, Barbara Santangelo, Chiara Pettinari, Giovanna Fontanella, Patrizia Fusco, L. Lacitignola, Adalberto Brach Del Prever, Gina Ancora, S. Amarri, Laura Lacitignola, Paola Sparano, Marcello Lanari, Stefano Gatti, Francesca Nesi, Valentina De Cosmi, Alessia Frimaire, A Lezo, Francesca Penagini, Carmen Di Scala, Giuseppina Migliore, Roberta Annibali, Grazia Di Leo, Paola Peverelli, Mara Salmaso, Antonella Lezo, Paola Melli, M. Pastore, E. Brunori, Claudia Banzato, M.I. Spagnuolo, Antonella Diamanti, G. Verlato, Angelo Campanozzi, Mariella Pace, Martina Biagioni, Graziano Memmini, Laura Mistura, Sergio Del Vecchio, Annalisa Famiani, Enrico Felici, Germana Casaccia, Graziana Galvagno, Mario Castello, R. Panceri, Paola Accorsi, Martina Fomasi, Francesca Cortinovis, Michela Perrone, Teresa Capriati, Andrea Chiaro, Silvio Ferraris, Nicola Cecchi, Maria Immacolata Spagnuolo, Patrizia Petitti, Cristina Malaventura, Maria Sangerardi, Enrico Gasparrini, Francesco Savino, Luigi Besenzon, Anna Meneghini, Azzurra Guerra, Alessandra Sala, Maria Magistã Anna, Enrico Aidala, Donata Scatã, Gianluigi Palamone, Tiziano Basso, Giuseppe Maggiore, A. Diamanti, Alessandra Mazzocchi, Alessia Morganti, Andreina Stamati Filomena, Paolo Siani, Roberto Panceri, Maria Pastore, Paolo Gandullia, Lezo, A., Diamanti, A., Capriati, T., Gandullia, P., Fiore, P., Lacitignola, L., Gatti, S., Spagnuolo, M. I., Cecchi, N., Verlato, G., Borodani, S., Forchielli, L., Panceri, R., Brunori, E., Pastore, M., Amarri, S., Abate, R., Accorsi, P., Aidala, E., Ancora, G., Angelotti, L., Annibali, R., Antonini Monica, A., Banzato, C., Barbaglia, M., Bardasi, G., Barrani, M., Basso, T., Brach del Prever, A., Belli, F., Bellomo Anna, R., Besenzon, L., Biagioni, M., Bonaudo, R., Bruni, G., Cagnoli, G., Campanozzi, A., Casaccia, G., Castello, M., Chiaro, A., Cimadore, N., Cioni, M., Cortinovis, F., De Cosmi, V., De Giacomo, C., Del Vecchio, S., Di Leo, G., Di Scala, C., Famiani, A., Felici, E., Ferraris, S., Fomasi, M., Fontanella, G., Frimaire, A., Fusco, P., Galvagno, G., Gasparrini, E., Guana, R., Guerra, A., Lanari, M., Lizzoli, F., Maggiore, G., Magista Anna, M., Malaventura, C., Marmetucci, L., Mazzocchi, A., Mazzoni, E., Melli, P., Memmini, G., Meneghini, A., Miglietti, N., Migliore, G., Mistura, L., Monaci, A., Morganti, A., Nesi, F., Opinto, V., Pace, M., Palamone, G., Parisi, G., Penagini, F., Perrone, M., Petitti, P., Pettinari, C., Peverelli, P., Pinon, M., Russo, C., Sala, A., Salata, M., Salmaso, M., Sangerardi, M., Santangelo, B., Savino, F., Scata, D., Siani, P., Sparano, P., Stamati Filomena, A., Tulli, M., Uga, E., Urbano, F., Zoppo, M., Zuin, G., Abate, Rosaria, Accorsi, Paola, Aidala, Enrico, Amarri, Sergio, Ancora, Gina, Angelotti, Luisella, Annibali, Roberta, Antonini Monica, Antonietta, Banzato, Claudia, Barbaglia, Michelangelo, Bardasi, Giulia, Barrani, Monica, Basso, Tiziano, Brach Del Prever, Adalberto, Belli, Fina, Bellomo Anna, Rita, Besenzon, Luigi, Biagioni, Martina, Bonaudo, Roberto, Bruni, Giulia, Brunori, Elena, Cagnoli, Giacomo, Campanozzi, Angelo, Casaccia, Germana, Castello, Mario, Chiaro, Andrea, Cimadore, Nicoletta, Cioni, Maddalena, Cortinovis, Francesca, De Cosmi, Valentina, De Giacomo, Costantino, Del Vecchio, Sergio, Diamanti, Antonella, Di Leo, Grazia, Di Scala, Carmen, Famiani, Annalisa, Felici, Enrico, Ferraris, Silvio, Fomasi, Martina, Fontanella, Giovanna, Frimaire, Alessia, Fusco, Patrizia, Galvagno, Graziana, Gandullia, Paolo, Gasparrini, Enrico, Guanã , Riccardo, Guerra, Azzurra, Lanari, Marcello, Lacitignola, Laura, Lezo, Antonella, Lizzoli, Francesca, Maggiore, Giuseppe, Magistã Anna, Maria, Malaventura, Cristina, Marmetucci, Luigi, Mazzocchi, Alessandra, Mazzoni, Elisa, Melli, Paola, Memmini, Graziano, Meneghini, Anna, Miglietti, Nunzia, Migliore, Giuseppina, Mistura, Laura, Monaci, Alessandro, Morganti, Alessia, Nesi, Francesca, Opinto, Vittoria, Pace, Mariella, Palamone, Gianluigi, Panceri, Roberto, Parisi, Giuseppe, Pastore, Maria, Penagini, Francesca, Perrone, Michela, Petitti, Patrizia, Pettinari, Chiara, Peverelli, Paola, Pinon, Michele, Russo, Carla, Sala, Alessandra, Salata, Michele, Salmaso, Mara, Sangerardi, Maria, Santangelo, Barbara, Savino, Francesco, Scatã , Donata, Siani, Paolo, Spagnuolo, Maria Immacolata, Sparano, Paola, Stamati Filomena, Andreina, Tulli, Monica, Uga, Elena, Urbano, Flavia, Verlato, Giovanna, Zoppo, Marisa, and Zuin, Giovanna
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0301 basic medicine ,Male ,Pediatrics ,Hospitalized patients ,Endocrinology, Diabetes and Metabolism ,Pediatric nutrition ,0302 clinical medicine ,Child Development ,Endocrinology ,Prevalence ,030212 general & internal medicine ,Growth Charts ,Child ,Nutritional support ,Wasting ,Growth Disorders ,Pediatric ,Stunting ,Nutrition and Dietetics ,Nutritional status ,Nutrition Surveys ,Diabetes and Metabolism ,Italy ,Malnutrition ,Child, Preschool ,Female ,medicine.symptom ,medicine.medical_specialty ,Adolescent ,Nutritional Status ,Socio-culturale ,Malnutrition in children ,03 medical and health sciences ,Young Adult ,medicine ,Humans ,030109 nutrition & dietetics ,business.industry ,Infant ,Anthropometry ,medicine.disease ,Parenteral nutrition ,Chronic Disease ,business ,Child, Hospitalized - Abstract
Introduction the prevalence of malnutrition in children and its impact on clinical outcomes is underrecognized by clinicians in Italy as well as worldwide. A novel definition of pediatric malnutrition has been recently proposed by a working group of the Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.), based on the correlation between illness and the use of zscores of anthropometric measurements. Aim to investigate the prevalence of malnutrition and related nutritional support among hospitalized children in Italy, in a nationwide survey performed in a single day (16/4/2015). Methods an open access website (http://nday.biomedia.net) was used to collected data from 73 hospitals and 101 wards in 14 Italian regions (1994 patients). Anonymous information was collected on hospitals' characteristics, patient's anthropometry, admission diagnosis, presence of chronic diseases and use of nutritional support: oral nutritional supplements (ONS), enteral nutrition (EN) or parenteral nutrition (PN). Z-scores of anthropometric measurements, calculated with Epi Info 7.1.5, defined nutritional status: wasting was identified by BMI or Weight-for-Length z-score (
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- 2017
19. Autosomal-dominant Alport syndrome: Natural history of a disease due to COL4A3 or COL4A4 gene
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Alessandra Renieri, Elena Bresin, Francesca Mari, Chiara Pescucci, Marco Seri, Rosanna Gusmano, Nunzia Miglietti, Cataldo Abaterusso, Paraskevi Vogiatzi, Elisa Scala, Rossella Caselli, Ilaria Longo, Pescucci C, Mari F, Longo I, Vogiatzi P, Caselli R, Scala E, Abaterusso C, Gusmano R, Seri M, Miglietti N, Bresin E, and Renieri A
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Adult ,Collagen Type IV ,Male ,Genetic counseling ,COL4A3 ,Nephritis, Hereditary ,ALPORT SYNDROME ,Kidney ,urologic and male genital diseases ,Asymptomatic ,Autoantigens ,medicine ,Humans ,COL4A4 ,Alport syndrome ,Microhematuria ,collagen IV genes ,Child ,COL4A3 gene ,Aged ,Genes, Dominant ,Genetics ,Aged, 80 and over ,incomplete penetrance ,Genetic heterogeneity ,business.industry ,COL4A4 gene ,Glomerulonephritis ,Middle Aged ,medicine.disease ,Penetrance ,medicine.icd_9_cm_classification ,Pedigree ,Phenotype ,inherited nephropathy ,Nephrology ,Mutation (genetic algorithm) ,Mutation ,phenotypic variability ,Female ,autosomal-dominant Alport syndrome ,medicine.symptom ,business - Abstract
Autosomal-dominant Alport syndrome: Natural history of a disease due to COL4A3 or COL4A4 gene. Background Alport syndrome is a clinically and genetically heterogeneous nephropathy. The majority of cases are transmitted as an X-linked semidominant condition due to COL4A5 mutations. In this form males are more severely affected than females. Less than 10% of cases are autosomal recessive due to mutation in either COL4A3 or COL4A4 . In this rarer form, both males and females are severely affected. Only two cases of autosomal-dominant Alport syndrome have been reported, one due to a COL4A3 mutation and the other due to a COL4A4 mutation. Because of the paucity of the reported families, the natural history of autosomal-dominant Alport syndrome is mostly unknown. Methods Four families with likely autosomal-dominant Alport syndrome were investigated. COL4A3 and COL4A4 genes were analyzed by denaturing high-performance liquid chromatography (HPLC). Automated sequencing was performed to identify the underlying mutation. Results Two families had a mutation in the COL4A4 gene and two in the COL4A3 . Accurate clinical evaluation of family members showed interesting results. Affected individuals (22 persons) had a wide range of phenotypes from end-stage renal disease (ESRD) in the fifth decade to a nonprogressive isolated microhematuria. Finally, three heterozygous individuals (90, 22 and 11years old, respectively) were completely asymptomatic. Conclusion This paper demonstrated that patients affected by autosomal-dominant Alport syndrome have a high clinical variability. Moreover, a reduced penetrance of about 90% (3 of 25) may be considered for the assessment of recurrence risk during genetic counseling of these families.
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- 2004
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20. Risk factors for poor renal prognosis in children with hemolytic uremic syndrome
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Angela Caringella, Elio Salvaggio, Laura De Petris, Leopoldo Peratoner, Maurizio Gaido, Lucilla Ravà, Alberto Edefonti, Alfredo Caprioli, Rosanna Coppo, Alfonso Ferretti, Giovanni Montini, Giovambattista Capasso, Gianfranco Rizzoni, Rosa Penza, Salvatore Li Volti, Alessandra Gianviti, Carmen Setzu, Gianluigi Ardissino, Nunzia Miglietti, Salvatore Maffei, Carmine Pecoraro, Alberto Eugenio Tozzi, Graziella Zacchello, Ilse Ratsche, Alberto Bettinelli, Silvio Maringhini, Marco Pennesi, Francesco Perfumo, Ivana Pela, Giuliana Lama, Tommaso De Palo, Gianviti, A, Tozzi, Ae, DE PETRIS, L, Caprioli, A, Rava, L, Edefonti, A, Ardissino, G, Montini, G, Zacchello, G, Ferretti, A, Pecoraro, C, DE PALO, T, Caringella, A, Gaido, M, Coppo, R, Perfumo, F, Miglietti, N, Ratsche, I, Penza, R, Capasso, Giovambattista, Maringhini, S, LI VOLTI, S, Setzu, C, Pennesi, M, Bettinelli, A, Peratoner, L, Pela, I, Salvaggio, E, Lama, G, Maffei, S, and Rizzoni, G.
- Subjects
Nephrology ,Diarrhea ,Male ,medicine.medical_specialty ,Atypical hemolytic uremic syndrome ,Adolescent ,medicine.medical_treatment ,Gastroenterology ,Shiga Toxin ,Cohort Studies ,Leukocyte Count ,fluids and secretions ,Shiga toxin-producing Escherichia coli ,Central Nervous System Diseases ,Risk Factors ,Internal medicine ,medicine ,Humans ,Risk factor ,Age of Onset ,Child ,Escherichia coli Infections ,Proportional Hazards Models ,Prognostic factor ,business.industry ,Proportional hazards model ,Infant ,Classification ,medicine.disease ,Prognosis ,Long-term outcome ,Survival Analysis ,Hemolytic urenic syndrome ,Treatment Outcome ,Italy ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Immunology ,Hemolytic-Uremic Syndrome ,Plasmapheresis ,Female ,medicine.symptom ,Age of onset ,business ,Kidney disease - Abstract
Many factors have been proposed as predictors of poor renal prognosis in children with hemolytic uremic syndrome (HUS), but their role is still controversial. Our aim was to detect the most reliable early predictors of poor renal prognosis to promptly identify children at major risk of bad outcome who could eventually benefit from early specific treatments, such as plasmapheresis. Prognostic factors identifiable at onset of HUS were evaluated by survival analysis and a proportional hazard model. These included age at onset, prodromal diarrhea (D), leukocyte count, central nervous system (CNS) involvement, and evidence of Shiga toxin-producing Escherichia coli (STEC) infection. Three hundred and eighty-seven HUS cases were reported; 276 were investigated for STEC infection and 189 (68%) proved positive. Age at onset, leukocyte count, and CNS involvement were not associated with the time to recovery. Absence of prodromal D and lack of evidence of STEC infection were independently associated with a poor renal prognosis; only 34% of patients D(-)STEC(- )recovered normal renal function compared with 65%-76% of D(+)STEC(+), D(+)STEC(-) and D(-)STEC(+ )patients. In conclusion, absence of both D and evidence of STEC infection are needed to identify patients with HUS and worst prognosis, while D(-) but STEC(+) patients have a significantly better prognosis.
- Published
- 2003
21. The genetic and clinical spectrum of a large cohort of patients with distal renal tubular acidosis.
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Palazzo V, Provenzano A, Becherucci F, Sansavini G, Mazzinghi B, Orlandini V, Giunti L, Roperto RM, Pantaleo M, Artuso R, Andreucci E, Bargiacchi S, Traficante G, Stagi S, Murer L, Benetti E, Emma F, Giordano M, Rivieri F, Colussi G, Penco S, Manfredini E, Caruso MR, Garavelli L, Andrulli S, Vergine G, Miglietti N, Mancini E, Malaventura C, Percesepe A, Grosso E, Materassi M, Romagnani P, and Giglio S
- Subjects
- Adolescent, Adult, Child, Child, Preschool, DNA Mutational Analysis, Female, Genetic Association Studies, Genetic Testing, Genotype, Hearing Loss, Sensorineural genetics, High-Throughput Nucleotide Sequencing, Humans, Infant, Male, Middle Aged, Mutation, Phenotype, Retrospective Studies, Young Adult, Acidosis, Renal Tubular genetics, Anion Exchange Protein 1, Erythrocyte genetics, Rare Diseases genetics, Renal Insufficiency, Chronic genetics, Vacuolar Proton-Translocating ATPases genetics
- Abstract
Primary distal renal tubular acidosis is a rare genetic disease. Mutations in SLC4A1, ATP6V0A4, and ATP6V1B1 genes have been described as the cause of the disease, transmitted as either an autosomal dominant or recessive trait. Particular clinical features, such as sensorineural hearing loss, have been mainly described in association with mutations in one gene instead of the others. Nevertheless, the diagnosis of distal renal tubular acidosis is essentially based on clinical and laboratory findings, and the series of patients described so far are usually represented by small cohorts. Therefore, a strict genotype-phenotype correlation is still lacking, and questions about whether clinical and laboratory data should direct the genetic analysis remain open. Here, we applied next-generation sequencing in 89 patients with a clinical diagnosis of distal renal tubular acidosis, analyzing the prevalence of genetic defects in SLC4A1, ATP6V0A4, and ATP6V1B1 genes and the clinical phenotype. A genetic cause was determined in 71.9% of cases. In our group of sporadic cases, clinical features, including sensorineural hearing loss, are not specific indicators of the causal underlying gene. Mutations in the ATP6V0A4 gene are quite as frequent as mutations in ATP6V1B1 in patients with recessive disease. Chronic kidney disease was frequent in patients with a long history of the disease. Thus, our results suggest that when distal renal tubular acidosis is suspected, complete genetic testing could be considered, irrespective of the clinical phenotype of the patient., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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22. Characterization of 28 novel patients expands the mutational and phenotypic spectrum of Lowe syndrome.
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Recker F, Zaniew M, Böckenhauer D, Miglietti N, Bökenkamp A, Moczulska A, Rogowska-Kalisz A, Laube G, Said-Conti V, Kasap-Demir B, Niemirska A, Litwin M, Siteń G, Chrzanowska KH, Krajewska-Walasek M, Sethi SK, Tasic V, Anglani F, Addis M, Wasilewska A, Szczepańska M, Pawlaczyk K, Sikora P, and Ludwig M
- Subjects
- Adolescent, Cataract diagnosis, Cataract genetics, Child, Child, Preschool, Chromosome Breakpoints, CpG Islands, DNA Mutational Analysis, Disease Progression, Europe epidemiology, Female, Genetic Predisposition to Disease, Heredity, Heterozygote, Humans, Hyperacusis diagnosis, Hyperacusis genetics, India epidemiology, Infant, Male, Oculocerebrorenal Syndrome epidemiology, Pedigree, Phenotype, Predictive Value of Tests, Prevalence, Renal Insufficiency, Chronic diagnosis, Renal Insufficiency, Chronic genetics, Thrombocytopenia diagnosis, Thrombocytopenia genetics, Time Factors, Young Adult, Mutation, Oculocerebrorenal Syndrome diagnosis, Oculocerebrorenal Syndrome genetics, Phosphoric Monoester Hydrolases genetics
- Abstract
Background: The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked multi-systemic disorder, almost always characterized by the triad of congenital cataract, cognitive and behavioral impairment and a proximal tubulopathy., Methods: Twenty-eight novel patients with suspected Lowe syndrome were studied., Results: All patients carried OCRL gene defects with mutational hot spots at CpG dinucleotides. Mutations previously unknown in Lowe syndrome were observed in ten of the 28 patients, and carriership was identified in 30.4 % of the mothers investigated. Mapping the exact breakpoints of a complete OCRL gene deletion revealed involvement of several flanking repeat elements. We noted a similar pattern of documented clinically relevant symptoms, and even though the patient cohort comprised relatively young patients, 32 % of these patients already showed advanced chronic kidney disease. Thrombocytopenia was seen in several patients, and hyperosmia and/or hyperacusis were reported recurrently. A p.Asp523Asn mutation in a Polish patient, associated with the typical cerebrorenal spectrum but with late cataract (10 year), was also evident in two milder affected Italian brothers with ocular involvement of similar progression., Conclusions: We have identified clinical features in 28 patients with suspected Lowe syndrome that had not been recognized in Lowe syndrome prior to our study. We also provide further evidence that OCRL mutations cause a phenotypic continuum with selective and/or time-dependent organ involvement. At least some of these mutants might exhibit a genotype-phenotype correlation.
- Published
- 2015
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23. Evidence of digenic inheritance in Alport syndrome.
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Mencarelli MA, Heidet L, Storey H, van Geel M, Knebelmann B, Fallerini C, Miglietti N, Antonucci MF, Cetta F, Sayer JA, van den Wijngaard A, Yau S, Mari F, Bruttini M, Ariani F, Dahan K, Smeets B, Antignac C, Flinter F, and Renieri A
- Subjects
- Adult, Aged, Female, Genetic Association Studies, Humans, Kidney metabolism, Kidney pathology, Male, Middle Aged, Mutation, Nephritis, Hereditary pathology, Pedigree, Autoantigens genetics, Collagen Type IV genetics, Nephritis, Hereditary genetics
- Abstract
Background: Alport syndrome is a clinically heterogeneous, progressive nephropathy caused by mutations in collagen IV genes, namely COL4A3 and COL4A4 on chromosome 2 and COL4A5 on chromosome X. The wide phenotypic variability and the presence of incomplete penetrance suggest that a simple Mendelian model cannot completely explain the genetic control of this disease. Therefore, we explored the possibility that Alport syndrome is under digenic control., Methods: Using massively parallel sequencing, we identified 11 patients who had pathogenic mutations in two collagen IV genes. For each proband, we ascertained the presence of the same mutations in up to 12 members of the extended family for a total of 56 persons studied., Results: Overall, 23 mutations were found. Individuals with two pathogenic mutations in different genes had a mean age of renal function deterioration intermediate with respect to the autosomal-dominant form and the autosomal-recessive one, in line with molecule stoichiometry of the disruption of the type IV collagen triple helix., Conclusions: Segregation analysis indicated three possible digenic segregation models: (i) autosomal inheritance with mutations on different chromosomes, resembling recessive inheritance (five families); (ii) autosomal inheritance with mutations on the same chromosome resembling dominant inheritance (two families) and (iii) unlinked autosomal and X-linked inheritance having a peculiar segregation (four families). This pedigree analysis provides evidence for digenic inheritance of Alport syndrome. Clinical geneticists and nephrologists should be aware of this possibility in order to more accurately assess inheritance probabilities, predict prognosis and identify other family members at risk., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
- Published
- 2015
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24. Cardiomyopathy in a male patient with neutropenia and growth delay.
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Folsi V, Miglietti N, Lombardi A, Boccacci S, Utyatnikova T, Donati C, Squassabia L, Gazzola L, Bosio I, Borghi A, Grassi V, Notarangelo LD, and Plebani A
- Subjects
- Acyltransferases, Barth Syndrome diagnosis, Barth Syndrome genetics, Cardiomyopathies genetics, DNA genetics, DNA Mutational Analysis, Diagnosis, Differential, Echocardiography, Genetic Predisposition to Disease, Growth Disorders genetics, Humans, Infant, Newborn, Male, Mutation, Radiography, Thoracic, Transcription Factors genetics, Abnormalities, Multiple, Cardiomyopathies diagnosis, Growth Disorders diagnosis, Neutropenia diagnosis
- Abstract
Neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, ranging from severe (<500 neutrophils/mm(3)) to mild (500-1500 neutrophils/mm(3)), which may also affect other organ systems such as the pancreas, central nervous system, heart, muscle and skin. Neutropenia can lead to life-threatening pyogenic infections whose severity is roughly inversely proportional to the circulating neutrophil counts.When neutropenia is detected, an attempt should be made to establish the etiology, and to distinguish acquired forms (the most frequent, including post viral neutropenia and autoimmune neutropenia) and congenital forms (rare disorders) that may be either isolated or part of a complex rare genetic disease. We report on a male patient initially diagnosed with isolated neutropenia who later turned out to be affected with Barth syndrome, a rare complex inherited disorder.
- Published
- 2014
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25. Human metapneumovirus infection in young children hospitalized with acute respiratory tract disease: virologic and clinical features.
- Author
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Caracciolo S, Minini C, Colombrita D, Rossi D, Miglietti N, Vettore E, Caruso A, and Fiorentini S
- Subjects
- Age Factors, Bronchiolitis virology, Child, Preschool, Comorbidity, Female, Genotype, Humans, Incidence, Infant, Male, Metapneumovirus classification, Metapneumovirus genetics, Nasal Cavity virology, Nasal Lavage Fluid, Paramyxoviridae Infections epidemiology, Paramyxoviridae Infections physiopathology, Phylogeny, Pneumonia virology, RNA, Viral genetics, Respiratory Syncytial Virus Infections complications, Respiratory Syncytial Virus Infections epidemiology, Respiratory Syncytial Viruses isolation & purification, Respiratory Tract Infections epidemiology, Respiratory Tract Infections physiopathology, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, Sequence Homology, Metapneumovirus isolation & purification, Paramyxoviridae Infections virology, Respiratory Tract Infections virology
- Abstract
Background: Human metapneumovirus (hMPV) is an emerging virus associated with acute respiratory tract infections (ARIs) in young children., Objectives: To evaluate virologic and clinical features of hMPV infection during 2 consecutive winter-spring seasons., Methods: Nasal washes were obtained from children younger than 5 years of age hospitalized for ARI. Specimens were tested for hMPV by reverse transcription-polymerase chain reaction. The hMPV F gene amplification products were sequenced, and phylogenetic trees were constructed., Results: A high incidence of hMPV infection (25.3%) was observed during the 2005-2006 winter-spring season, whereas a much lower rate of infection (4.7%) during the following season was found. Phylogenetic analysis revealed that, during the 2 seasons, 60.4% of the hMPV detected were A2a, 22.9% were A2b, 4.2% were B1, and 12.5% were B2. hMPV A1 strains were not detected in any tested specimen. Clinical diagnosis was bronchiolitis in 57.1%; pneumonia in 25%; and a upper respiratory tract illness in 17.8%. Bronchiolitis was more frequent in children less than 1 year of age (80%) than in children more than 1 year of age (30.8%) (P < 0.05). When hMPV was found frequently, the hMPV spread overlapped with that of respiratory syncytial virus (RSV) and hMPV/RSV coinfections were common events (19 of 39; 48.7%). hMPV/RSV-coinfected children developed pneumonia more frequently than hMPV-infected patients (57.9% versus 20%) but no differences in disease severity (gauged by duration of hospitalization and requirement of oxygen) were observed., Conclusions: These results provide further evidence of the importance of hMPV as a pathogen associated with ARI in young children. Involvement of hMPV/RSV coinfection in cases of pneumonia is suspected.
- Published
- 2008
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26. Autosomal-dominant Alport syndrome: natural history of a disease due to COL4A3 or COL4A4 gene.
- Author
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Pescucci C, Mari F, Longo I, Vogiatzi P, Caselli R, Scala E, Abaterusso C, Gusmano R, Seri M, Miglietti N, Bresin E, and Renieri A
- Subjects
- Adult, Aged, Aged, 80 and over, Child, Female, Genes, Dominant, Humans, Kidney pathology, Male, Middle Aged, Mutation, Nephritis, Hereditary etiology, Nephritis, Hereditary pathology, Pedigree, Phenotype, Autoantigens genetics, Collagen Type IV genetics, Nephritis, Hereditary genetics
- Abstract
Background: Alport syndrome is a clinically and genetically heterogeneous nephropathy. The majority of cases are transmitted as an X-linked semidominant condition due to COL4A5 mutations. In this form males are more severely affected than females. Less than 10% of cases are autosomal recessive due to mutation in either COL4A3 or COL4A4. In this rarer form, both males and females are severely affected. Only two cases of autosomal-dominant Alport syndrome have been reported, one due to a COL4A3 mutation and the other due to a COL4A4 mutation. Because of the paucity of the reported families, the natural history of autosomal-dominant Alport syndrome is mostly unknown., Methods: Four families with likely autosomal-dominant Alport syndrome were investigated. COL4A3 and COL4A4 genes were analyzed by denaturing high-performance liquid chromatography (HPLC). Automated sequencing was performed to identify the underlying mutation., Results: Two families had a mutation in the COL4A4 gene and two in the COL4A3. Accurate clinical evaluation of family members showed interesting results. Affected individuals (22 persons) had a wide range of phenotypes from end-stage renal disease (ESRD) in the fifth decade to a nonprogressive isolated microhematuria. Finally, three heterozygous individuals (90, 22 and 11 years old, respectively) were completely asymptomatic., Conclusion: This paper demonstrated that patients affected by autosomal-dominant Alport syndrome have a high clinical variability. Moreover, a reduced penetrance of about 90% (3 of 25) may be considered for the assessment of recurrence risk during genetic counseling of these families.
- Published
- 2004
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27. Risk factors for poor renal prognosis in children with hemolytic uremic syndrome.
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Gianviti A, Tozzi AE, De Petris L, Caprioli A, Ravà L, Edefonti A, Ardissino G, Montini G, Zacchello G, Ferretti A, Pecoraro C, De Palo T, Caringella A, Gaido M, Coppo R, Perfumo F, Miglietti N, Ratsche I, Penza R, Capasso G, Maringhini S, Li Volti S, Setzu C, Pennesi M, Bettinelli A, Peratoner L, Pela I, Salvaggio E, Lama G, Maffei S, and Rizzoni G
- Subjects
- Adolescent, Age of Onset, Central Nervous System Diseases complications, Child, Child, Preschool, Cohort Studies, Diarrhea epidemiology, Escherichia coli Infections complications, Escherichia coli Infections epidemiology, Escherichia coli Infections metabolism, Female, Hemolytic-Uremic Syndrome pathology, Humans, Infant, Italy epidemiology, Leukocyte Count, Male, Prognosis, Proportional Hazards Models, Risk Factors, Shiga Toxin metabolism, Survival Analysis, Treatment Outcome, Hemolytic-Uremic Syndrome epidemiology
- Abstract
Many factors have been proposed as predictors of poor renal prognosis in children with hemolytic uremic syndrome (HUS), but their role is still controversial. Our aim was to detect the most reliable early predictors of poor renal prognosis to promptly identify children at major risk of bad outcome who could eventually benefit from early specific treatments, such as plasmapheresis. Prognostic factors identifiable at onset of HUS were evaluated by survival analysis and a proportional hazard model. These included age at onset, prodromal diarrhea (D), leukocyte count, central nervous system (CNS) involvement, and evidence of Shiga toxin-producing Escherichia coli (STEC) infection. Three hundred and eighty-seven HUS cases were reported; 276 were investigated for STEC infection and 189 (68%) proved positive. Age at onset, leukocyte count, and CNS involvement were not associated with the time to recovery. Absence of prodromal D and lack of evidence of STEC infection were independently associated with a poor renal prognosis; only 34% of patients D(-)STEC(- )recovered normal renal function compared with 65%-76% of D(+)STEC(+), D(+)STEC(-) and D(-)STEC(+ )patients. In conclusion, absence of both D and evidence of STEC infection are needed to identify patients with HUS and worst prognosis, while D(-) but STEC(+) patients have a significantly better prognosis.
- Published
- 2003
- Full Text
- View/download PDF
28. Broadening the spectrum of diseases related to podocin mutations.
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Caridi G, Bertelli R, Di Duca M, Dagnino M, Emma F, Onetti Muda A, Scolari F, Miglietti N, Mazzucco G, Murer L, Carrea A, Massella L, Rizzoni G, Perfumo F, and Ghiggeri GM
- Subjects
- Actinin genetics, Adolescent, Child, Child, Preschool, DNA Mutational Analysis, Exons, Female, Gene Frequency, Genetic Predisposition to Disease epidemiology, Glomerulosclerosis, Focal Segmental epidemiology, Glomerulosclerosis, Focal Segmental genetics, Heterozygote, Homozygote, Humans, Incidence, Infant, Infant, Newborn, Intracellular Signaling Peptides and Proteins, Male, Nephrotic Syndrome epidemiology, Phenotype, Proteins genetics, Proteinuria epidemiology, Proteinuria genetics, Membrane Proteins genetics, Microfilament Proteins, Nephrotic Syndrome genetics
- Abstract
A total of 179 children with sporadic nephrotic syndrome were screened for podocin mutations: 120 with steroid resistance, and 59 with steroid dependence/frequent relapses. Fourteen steroid-resistant patients presented homozygous mutations that were associated with early onset of proteinuria and variable renal lesions, including one case with mesangial C3 deposition. Single mutations of podocin were found in four steroid-resistant and in four steroid-dependent; five patients had the same mutation (P20L). Among these, two had steroid/cyclosporin resistance, two had steroid dependence, and one responded to cyclosporin. The common variant R229Q of podocin, recently associated with late-onset focal segmental glomerulosclerosis, had an overall allelic frequency of 4.2% versus 2.5% in controls. To further define the implication of R229Q, a familial case was characterized with two nephrotic siblings presenting the association of the R229Q with A297V mutation that were inherited from healthy mother and father, respectively. Immunohistochemistry with anti-podocin antibodies revealed markedly decreased expression of the protein in their kidneys. All carriers of heterozygous coding podocin mutation or R229Q were screened for nephrin mutation that was found in heterozygosity associated with R229Q in one patient. Finally, podocin loss of heterozygosity was excluded in one heterozygous child by characterizing cDNA from dissected glomeruli. These data outline the clinical features of sporadic nephrotic syndrome due to podocin mutations (homozygous and heterozygous) in a representative population with broad phenotype, including patients with good response to drugs. The pathogenetic implication of single podocin defects per se in proteinuria must be further investigated in view of the possibility that detection of a second mutation could have been missed. A suggested alternative is the involvement of other gene(s) or factor(s).
- Published
- 2003
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29. Identification of fifteen novel mutations in the SLC12A3 gene encoding the Na-Cl Co-transporter in Italian patients with Gitelman syndrome.
- Author
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Syrén ML, Tedeschi S, Cesareo L, Bellantuono R, Colussi G, Procaccio M, Alì A, Domenici R, Malberti F, Sprocati M, Sacco M, Miglietti N, Edefonti A, Sereni F, Casari G, Coviello DA, and Bettinelli A
- Subjects
- Alkalosis blood, Alkalosis urine, Calcium urine, DNA chemistry, DNA genetics, Humans, Hypokalemia blood, Hypokalemia urine, Italy, Magnesium blood, Mutation, Mutation, Missense, Polymorphism, Single-Stranded Conformational, Sequence Analysis, DNA, Sequence Deletion, Sodium Chloride Symporters, Solute Carrier Family 12, Member 3, Syndrome, Alkalosis genetics, Carrier Proteins genetics, Hypokalemia genetics, Receptors, Drug, Symporters
- Abstract
The SLC12A3 gene encodes the thiazide-sensitive Na-Cl co-transporter (NCCT) expressed in the apical membrane of the distal convoluted tubule of the kidney. Inactivating mutations of this gene are responsible for Gitelman syndrome (GS), a disorder inherited as an autosomal recessive trait. We searched for SLC12A3 gene mutations in 21 Italian patients with the clinical and biochemical features of GS (hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria, and the absence of nephrocalcinosis). All coding regions with their intron-exon boundaries were analyzed using PCR and SSCP techniques followed by sequencing analysis. We identified 21 different mutations evenly distributed throughout the gene without any mutation hot-spot. Fifteen are novel variants, including 12 missense mutations, one deletion, one deletion-insertion and one splice site mutation: R158Q, T163M, W172R, G316V, G374V, G463E, A464T, S615W, V677M, R852S, R958G, C985Y, 2114-2120delACCAAGT, 2144-2158delGCCTTCTACTCGGATinsTG, and 531-2A>G., (Copyright 2002 Wiley-Liss, Inc.)
- Published
- 2002
- Full Text
- View/download PDF
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