27 results on '"Presi S"'
Search Results
2. Genetic surfactant dysfunction in newborn infants and children with acute and chronic lung disease
- Author
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Somaschini, M, Presi, S, Ferrari, M, Vergani, B, Carrera, P, Somaschini, Marco, Presi, Silvia, Ferrari, Maurizio, Vergani, Barbara, Carrera, Paola, Somaschini, M, Presi, S, Ferrari, M, Vergani, B, and Carrera, P
- Subjects
interstitial lung disease ,Respiratory distress syndrome ,genetic basis of disease ,lcsh:R ,Surfactant protein ,lcsh:RJ1-570 ,lcsh:Medicine ,lcsh:Pediatrics ,Interstitial lung disease ,ABCA3 ,Genetic basis of disease ,surfactant proteins ,Newborn ,respiratory distress syndrome ,newborn ,Pediatrics, Perinatology and Child Health ,abca3 - Abstract
Mutations in genes encoding surfactant protein B (SP-B), ATP-binding cassette transporter A3 (ABCA3) and surfactant protein C (SP-C) can result in neonatal and pediatric lung disease. We retrospectively reviewed 391 molecular analyses of genes encoding SP-B (SFTPB), SP-C (SFTPC) and ABCA3 (ABCA3) performed in our laboratory from 2000 to 2015 in term and preterm newborn infants with severe respiratory distress syndrome (RDS), infants and children with interstitial lung disease (ILD), chorionic villi for prenatal diagnosis, parents and siblings of affected infants. Direct sequencing of SFTPB, SFTPC and ABCA3 was performed on genomic DNA extracted from peripheral blood. Histopathologic, immunohistochemical and ultrastructural analyses were performed when lung tissue was available. Genetic variants in SFTPB, SFTPC, ABCA3 were identified in 71 of 181 (39%) term and preterm newborn infants tested for severe and unexplained RDS and in 38 of 74 (51%) infants and children with ILD. A higher mortality rate was recorded among term newborn infants with homozygous or compound heterozygous mutations in SFTPB and ABCA3. Light microscopy and immunohistochemical analysis of the lung tissue were performed in 11 infants and electron microscopy in 8. Prenatal diagnosis was performed in 8 women with a previous child who died because of ABCA3 deficiency; 2 fetuses affected, 5 carriers and 1 normal were identified. Surfactant dysfunction was identified in a significant number of newborn infants with severe unexplained respiratory failure and children with ILD, indicating the importance of genetic studies in infants and children with this phenotype. While actual treatment is primarily supportive, early identification is important to establish appropriate management and evaluation of treatment options and to offer genetic counselling and prenatal diagnosis.
- Published
- 2017
3. Deep tissue biopsy vs. superficial swab culture monitoring in the microbiological assessment of limb-threatening diabetic foot infection
- Author
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Pellizzer, G., Strazzabosco, M., Presi, S., Furlan, F., Lora, L., Benedetti, P., Bonato, M., Erle, G., and de Lalla, F.
- Published
- 2001
4. Fatal respiratory failure in a full-term newborn with two ABCA3 gene mutations: a case report
- Author
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Ciantelli, M, primary, Ghirri, P, additional, Presi, S, additional, Sigali, E, additional, Vuerich, M, additional, Somaschini, M, additional, Ferrari, M, additional, Boldrini, A, additional, and Carrera, P, additional
- Published
- 2010
- Full Text
- View/download PDF
5. Phylogenetic internal control for HIV-1 genotypic antiretroviral testing
- Author
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Boeri, E., Canducci, F., Carrera, P., Massimo Clementi, Grasso, M. A., Presi, S., Racca, S., Boeri, E, Canducci, E, Grasso, Ma, Presi, S, Carrera, P, Racca, S, and Clementi, Massimo
- Subjects
Quality Control ,Base Sequence ,Genotype ,Anti-HIV Agents ,Sequence Homology ,HIV Infections ,Microbial Sensitivity Tests ,HIV Reverse Transcriptase ,HIV Protease ,Drug Resistance, Viral ,HIV-1 ,Humans ,Amino Acid Sequence ,Phylogeny - Abstract
Genotypic testing includes several steps (RNA purification, RT-PCR amplification, DNA sequencing, sequence editing and analysis) that should be individually controlled. In our laboratory, we have added to this step-by-step internal control a final phylogenetic quality control: this is performed every time a sequence is obtained from a patient previously subjected to the same test. Each sequence with this characteristic is routinely compared with sequences from previous samples of the same patient by multiple alignment and a neighbor-joining tree by using Kimura two-parameter method is constructed. To validate the quality control procedure, we have aligned and calculated the mean similarity of the reverse transcriptase (first 984 nucleotides) and protease (whole gene) sequences from 30 patients whose virus was completely wild-type for both reverse transcriptase and protease. In the same tree, we have added the sequences obtained from 5 out of the 30 patients, tested at a second time point. The wild type sequences have shown a mean inter-sample divergence of 2.9%, and all the sequence pairs from individual patients clustered together in the tree constructed with the nucleotide sequences, while the tree constructed with the inferred aminoacid sequences did not always permit to cluster the sequences from the same patients. This indicates that: 1) the phylogenetic analysis of nucleic acid sequences can be useful to rule out sample mix-up; 2) the belonging of a sequence to each individual patient can efficiently be assessed also in the cases of extreme divergence in terms of drug resistance mutations.
6. Study on mutations and antiretroviral therapy (SMART): Preliminary results
- Author
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Nicola Gianotti, Moretti, F., Tambussi, G., Racca, S., Presi, S., Crucianelli, R., Carrera, P., Ferrari, M., and Lazzarin, A.
7. Integration of multigene panels for the diagnosis of hereditary retinal disorders using Next Generation Sequencing and bioinformatics approaches
- Author
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Di Resta, C., Spiga, I., Presi, S., Merella, S., Pipitone, G. B., Manitto, M. P., Querques, G., Parodi, M. B., Ferrari, M., Paola Carrera, Di Resta, Chiara, Spiga, Ivana, Presi, Silvia, Merella, Stefania, Pipitone, Giovanni Battista, Manitto, Maria Pia, Querques, Giuseppe, Battaglia Parodi, Maurizio, Ferrari, Maurizio, and Carrera, Paola
- Subjects
NGS ,diagnostic yield ,multigene panels ,inherited retinal dystrophie - Abstract
In recent years, Next-Generation Sequencing (NGS) opened a new way for the study of pathogenic mechanisms and for molecular diagnosis of inherited disorders. In the present work, we focused our attention on the inherited retinal dystrophies (IRDs), a group of specific disorders of the retina, displaying a very high clinical and genetic heterogeneity, whose genetic diagnosis is not easily feasible. It represents a paradigmatic example for the integration of clinical and molecular examination toward precision medicine. In this paper, we discuss the use of targeted NGS resequencing of selected gene panels in a cohort of patients affected by IRDs. We tested the hypothesis to apply a selective approach based on a careful clinical examination. By this approach we reached a 66% overall detection rate for pathogenic variants, with a 52% diagnostic yield. Reduction of the efforts for validation and classification of variants is a clear advantage for the management of genetic testing in a clinical setting.
8. Molecular analysis of cerebrospinal fluid: potential for the study of HIV-1 infection of the central nervous system
- Author
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Paola Cinque, Bestetti, A., Morelli, P., and Presi, S.
9. Definition and management of colorectal polyposis not associated with APC/MUTYH germline pathogenic variants: AIFEG consensus statement
- Author
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Emanuele Damiano Luca Urso, Maurizio Ponz de Leon, Marco Vitellaro, Guglielmo Niccolò Piozzi, Quoc Riccardo Bao, Aline Martayan, Andrea Remo, Vittoria Stigliano, Cristina Oliani, Emanuela Lucci Cordisco, Salvatore Pucciarelli, Guglielmina Nadia Ranzani, Alessandra Viel, Francesca Adami, Elisa Alducci, Lucia Amadori, Valentina Arcangeli, Luisa Balestrino, Daniela Barana, Lucio Bertario, Bernardo Bonanni, Stefania Boni, Pierluigi Bullian, Fiorella Carbonardi, Ileana Carnevali, Paola Castelli, Francesco Celotto, Giulia Cini, Gino Crivellari, Duilio Della Libera, Anastasia Dell'elice, Maria Digennaro, Alessandra D'urso, Antonella Fabretto, Daniele Fanale, Irene Feroce, Daniela Furlan, Paola Ghiorzo, Mara Giacché, Milena Gusella, Barbara Liserre, Isabella Mammi, Stefania Massuras, Daniela Mazzà, Eleonora Mollica, Alberto Morabito, Giorgia Nardo, Flavia Palermo, Elena Panizza, Margherita Patruno, Monica Pedroni, Valeria Grazia Maria Pensotti, Guglielmo Niccolo Piozzi, Simonetta Pozzi, Silvia Presi, Marta Puzzono, Mila Ravegnani, Maria Teresa Ricci, Luca Roncucci, Giovanni Battsita Rossi, Elena Maria Sala, Lupe Sanchez Mete, Daniele Sandonà, Stefania Sciallero, Davide Serrano, Stefano Signoroni, Francesca Spina, Monica Taborelli, Gianluca Tedaldi, Maria Grazia Tibiletti, Silvia Tognazzo, Gianluca Tolva, Cristina Maria Concetta Trovato, Daniela Turchetti, Dora Varvara, Caterina Vivanet, Stefania Zovato, Raffaella Alessia Zuppardo, Urso E.D.L., Ponz de Leon M., Vitellaro M., Piozzi G.N., Bao Q.R., Martayan A., Remo A., Stigliano V., Oliani C., Lucci Cordisco E., Pucciarelli S., Ranzani G.N., Viel A., Adami F., Alducci E., Amadori L., Arcangeli V., Balestrino L., Barana D., Bertario L., Bonanni B., Boni S., Bullian P., Carbonardi F., Carnevali I., Castelli P., Celotto F., Cini G., Crivellari G., Libera D.D., Dell'elice A., Digennaro M., D'urso A., Fabretto A., Fanale D., Feroce I., Furlan D., Ghiorzo P., Giacche M., Gusella M., Liserre B., Mammi I., Massuras S., Mazza D., Mollica E., Morabito A., Nardo G., Palermo F., Panizza E., Patruno M., Pedroni M., Pensotti V.G.M., Pozzi S., Presi S., Puzzono M., Ravegnani M., Ricci M.T., Roncucci L., Rossi G.B., Sala E.M., Mete L.S., Sandona D., Sciallero S., Serrano D., Signoroni S., Spina F., Taborelli M., Tedaldi G., Tibiletti M.G., Tognazzo S., Tolva G., Trovato C.M.C., Turchetti D., Varvara D., Vivanet C., Zovato S., and Zuppardo R.A.
- Subjects
Oncology ,medicine.medical_specialty ,Gastrointestinal tumors ,Colorectal cancer ,Surgical Management ,Colorectal polyposis ,Germline ,03 medical and health sciences ,Cancer Genetic ,0302 clinical medicine ,MUTYH ,Internal medicine ,medicine ,Cancer Genetics ,Polyposis coli ,Hepatology ,Pathogenic mutation ,business.industry ,Colorectal polyposis not associated with APC/MUTYH mutation ,Polyposis management guideline ,Gastroenterology ,Expert consensus ,Endoscopic surveillance ,medicine.disease ,Consensus development conference ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,business - Abstract
An expert consensus panel convened by the Italian Association for Inherited and Familial Gastrointestinal Tumors (Associazione Italiana per lo Studio della Familiarita ed Ereditarieta dei Tumori Gastrointestinali, AIFEG) reviewed the literature and agreed on a number of position statements regarding the definition and management of polyposis coli without an identified pathogenic mutation on the APC or MUTYH genes, defined in the document as NAMP (non-APC/MUTYH polyposis).
- Published
- 2021
10. Novel JAG1 Deletion Variant in Patient with Atypical Alagille Syndrome
- Author
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Emanuela T Locati, Silvia Presi, Paola Carrera, Mario Carminati, Michelle M. Monasky, Barbara Pirola, Emanuele Micaglio, Alessandro Giamberti, Maurizio Ferrari, Andreea Alina Andronache, Carlo Pappone, Micaglio, E., Andronache, A. A., Carrera, P., Monasky, M. M., Locati, E. T., Pirola, B., Presi, S., Carminati, M., Ferrari, M., Giamberti, A., and Pappone, C.
- Subjects
Male ,0301 basic medicine ,Pathology ,Genetic testing ,Heart disease ,Case Report ,030105 genetics & heredity ,neural tube defect ,jaundice ,Electrocardiography ,Ductus arteriosus ,Alagille syndrome ,Variant ,Pulmonary branche ,Spectroscopy ,Neural tube defect ,Heart ,General Medicine ,Hypoplasia ,Pedigree ,Computer Science Applications ,medicine.anatomical_structure ,Liver ,Cholestasi ,Female ,bilirubin ,Pulmonary atresia ,Cardiac ,JAG1 ,Human ,medicine.medical_specialty ,cardiac ,Jaundice ,heart ,Pulmonary Artery ,liver ,Catalysis ,genetic testing ,Inorganic Chemistry ,03 medical and health sciences ,medicine ,Physical and Theoretical Chemistry ,Craniofacial ,Molecular Biology ,hypoplasia ,Cyanosi ,Base Sequence ,business.industry ,cyanosis ,Organic Chemistry ,Infant, Newborn ,Bilirubin ,medicine.disease ,030104 developmental biology ,variant ,pulmonary branches ,Mutation ,mutation ,cholestasis ,business ,Jagged-1 Protein ,Gene Deletion - Abstract
Alagille syndrome (AGS) is an autosomal-dominant disorder characterized by various degrees of abnormalities in the liver, heart, eyes, vertebrae, kidneys, face, vasculature, skeleton, and pancreas. This case report describes a newborn child exhibiting a congenital neural tube defect and peculiar craniofacial appearance characterized by a prominent forehead, deep-set eyes, bulbous nasal tip, and subtle upper lip. Just a few hours after birth, congenital heart disease was suspected for cyanosis and confirmed by heart evaluation. In particular, echocardiography indicated pulmonary atresia with ventricular septal defect with severe hypoplasia of the pulmonary branches (1.5 mm), large patent ductus arteriosus and several major aortopulmonary collateral arteries. Due to the association of peculiar craniofacial appearance and congenital heart disease, a form of Alagille syndrome was suspected. In addition, on the fifth day after birth, the patient developed jaundice, had acholic stools, and high levels of conjugated bilirubin and gamma-glutamyltransferase (GGT) were detected in the blood. Genetic testing revealed the novel variant c.802del in a single copy of the JAG1 gene. No variants in the NOTCH2 gene were detected. To the best of our knowledge, this is the first clinical description of a congenital neural tube defect in a molecularly confirmed Alagille patient. This work demonstrates a novel pathogenic heterozygous JAG1 mutation is associated with an atypical form of Alagille syndrome, suggesting an increased risk for neural tube defects compared to other Alagille patients.
- Published
- 2019
11. Null ABCA3 in humans: Large homozygous ABCA3 deletion, correlation to clinical-pathological findings
- Author
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Carrera, Paola, Ferrari, Maurizio, Presi, Silvia, Ventura, Luisa, Vergani, Barbara, Lucchini, Valeria, Cogo, Paola, Carnielli, Virgilio P., Somaschini, Marco, Tagliabue, Paolo, Carrera, P, Ferrari, Maurizio, Presi, S, Ventura, L, Vergani, B, Lucchini, V, Cogo, Pe, Carnielli, Vp, Somaschini, M, Tagliabue, P., Ferrari, M, Cogo, P, Carnielli, V, and Tagliabue, P
- Subjects
Lung Diseases ,Pulmonary and Respiratory Medicine ,patient care management ,Sibling ,ATP-Binding Cassette Transporter ,ABCA3 ,Pediatrics ,Fatal Outcome ,newborn ,molecular diagnostic testing ,Humans ,Southern ,respiratory distress syndrome ,sequence deletion ,ATP-Binding Cassette Transporters ,Blotting, Southern ,Female ,Homozygote ,Infant, Newborn ,Lung Diseases, Interstitial ,Respiratory Distress Syndrome, Newborn ,Sequence Analysis, DNA ,Gene Deletion ,Siblings ,Pediatrics, Perinatology and Child Health ,Blotting ,Infant ,DNA ,Perinatology and Child Health ,Interstitial ,Sequence Analysis ,Human - Abstract
A study was undertaken to analyze the clinical presentation, pulmonary function, and pathological features in two female siblings with neonatal pulmonary surfactant metabolism dysfunction, type 3 (MIM 610921). The clinical records of the siblings were examined; the genes encoding surfactant protein B (SFTPB), surfactant protein C (SFTPC), and ATP-binding cassette transporter 3 protein (ABCA3) were analyzed with direct sequencing and Southern blotting. The infants were homozygous for a 5,983bp deletion in ABCA3 including exons 2-5 as well as the start AUG codon and a putative Golgi exit signal motif. Dense abnormalities of lamellar bodies at electron microscopy and absence of ABCA3 at immunohistochemical staining were in agreement with the presence of two null alleles. In addition, an increased lipid synthesis suggested a compensatory mechanism. The clinical course in the two sisters was influenced by different environmental factors like the time needed for molecular confirmation, the ventilatory assistance adopted, the occurrence of infections. A less aggressive clinical approach did not improve the course of the disease; the prognosis was always poor. Development of a fast molecular test, able to detect also structural variants, is needed. Pediatr Pulmonol. � 2014 Wiley Periodicals, Inc.
- Published
- 2014
12. Fatal respiratory failure in a full-term newborn with two ABCA3 gene mutations: a case report
- Author
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Maurizio Ferrari, M Vuerich, Antonio Boldrini, Massimiliano Ciantelli, Marco Somaschini, Paolo Ghirri, Emilio Sigali, Silvia Presi, Paola Carrera, Ciantelli, M, Ghirri, P, Presi, S, Sigali, E, Vuerich, M, Somaschini, M, Ferrari, Maurizio, Boldrini, A, and Carrera, P.
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Gene mutation ,ABCA3 ,Fatal Outcome ,Recurrence ,medicine ,Humans ,Treatment Failure ,Gene ,Full Term ,Respiratory Distress Syndrome, Newborn ,Respiratory distress ,biology ,Continuous Positive Airway Pressure ,business.industry ,Infant, Newborn ,Obstetrics and Gynecology ,Virology ,Phenotype ,Adenosine ,Respiratory failure ,Pediatrics, Perinatology and Child Health ,Mutation ,Retreatment ,biology.protein ,ATP-Binding Cassette Transporters ,Radiography, Thoracic ,business ,Respiratory Insufficiency ,Tomography, X-Ray Computed ,medicine.drug - Abstract
Genetic mutations associated with pulmonary surfactant protein deficiency are associated with diverse clinical phenotypes. Mutations of the surfactant protein B and C genes were the first to be described. In 2004, fatal surfactant deficiency in newborns due to mutations of the gene encoding the adenosine triphosphate-binding cassette transporter A3 (ABCA3) was first reported. Few cases of lethal adenosine triphosphate-binding cassette transporter A3 mutations have been described to date. In our report, we describe a full-term newborn that died because of respiratory failure secondary to an uncommon ABCA3 genetic configuration.
- Published
- 2011
13. Germline pathogenic variants of cancer predisposition genes in a multicentre Italian cohort of pancreatic cancer patients.
- Author
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Orsi G, Carconi C, Ghiorzo P, Carrera P, Pastorino L, Presi S, Chiaravalli M, Barbieri E, Giordano G, Sciallero S, Puccini A, Salvatore L, Cortesi L, Macchini M, Natalicchio MI, Allavena E, Pirrone C, Archibugi L, Dalmasso B, Bruno W, Tortora G, Landriscina M, Capurso G, Cascinu S, Falconi M, and Reni M
- Subjects
- Humans, Male, Female, Italy epidemiology, Middle Aged, Aged, Adult, Aged, 80 and over, Ataxia Telangiectasia Mutated Proteins genetics, Checkpoint Kinase 2, Germ-Line Mutation, Pancreatic Neoplasms genetics, Genetic Predisposition to Disease
- Abstract
Background and Aim: Germline BRCA1-2 test is routinely recommended in Pancreatic Cancer (PC) patients, due to its clinical-epidemiological relevance. Data on the prevalence of germline pathogenic variants (gPV) in other cancer predisposition and DNA Damage Repair (DDR) system-related genes in unselected PC cases are sparce in Italy. We assessed this prevalence in a multicentre cohort, to derive recommendations for PC patients., Methods: Clinical data of 1200 consecutive PC patients, of any age and stage, tested with a multigene germline panel were collected. A descriptive analysis of gPV frequency and clinical variables was performed both in 1092 patients tested for an 18 genes core-panel (CP-18 cohort) and in 869 patients screened only for CDKN2A., Results: 11.5 % (126/1092) of CP-18 cohort patients harbored a gPV in ≥ 1 gene. Highest gPV frequencies were detected in ATM (3.1 %), BRCA2 (2.9 %), BRCA1 (1.6 %), CHEK2 (1.1 %). Patients harboring any CP-18 gene and BRCA1-2 gPV were younger and with a higher rate of personal (PH) or family history (FH) of cancer when compared to no gPV patients. The risk of having a gPV was ≥ 7 % in all subgroups of patients, including those aged > 73, with tumor stage I-III and negative FH/PH. CDKN2A gPV were detected in 2.6 % (23/869) of patients., Conclusions: A remarkable prevalence of gPV in cancer predisposition and DDR genes is reported in this large multicentre cohort of consecutive and unselected PC patients. Therefore, we recommend multigene germline testing (at least including BRCA1-2, ATM, CDKN2A, PALB2) for all PC patients, irrespective of age, stage, PH/FH., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Stefania Sciallero: Michele Reni: All remaining authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
14. Germline testing and genetic counseling in biliary tract cancer: an operative proposal to improve the state of art.
- Author
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Rimini M, Presi S, Pipitone GB, Russo Raucci A, Ratti F, Della Corte A, Pedica F, Vanella G, Tonon G, Burgio V, Vitiello F, Rossari F, Amadeo E, Maria Giulia C, Pecciarini L, Arcidiacono PG, Falcinelli F, Cascinu S, De Cobelli F, Aldrighetti L, Patricelli MG, Carrera P, and Casadei-Gardini A
- Subjects
- Humans, Biomarkers, Tumor genetics, Phenotype, Predictive Value of Tests, Risk Factors, Biliary Tract Neoplasms genetics, Biliary Tract Neoplasms therapy, Genetic Counseling, Genetic Predisposition to Disease, Genetic Testing, Germ-Line Mutation
- Abstract
Introduction: A genetic predisposition seems to be involved in biliary tract cancer, but the prevalence of germline mutations in BTC remains unclear, and the therapeutic role of the germline pathologic variants is still unknown., Area Covered: The aim of the present work is to systematically review the data available on the hereditary predisposition of biliary tract cancer by a specific research on PubMed, in order to highlight the most important critical points and to define the current possible role of germinal testing and genetic counseling in this setting of patients., Expert Opinion: Basing on data already available, we decided to start in our institution a specific genetic protocol focused on biliary tract cancer patients, which includes genetic counseling and, if indicated, germline test. The inclusion criteria are: 1) Patient with personal history of oncologic disease other than BTC, 2) Patient with familiar history of oncologic disease (considering relatives of first and second grade), 3) Patient with ≤ 50 years old, 4) Patient presenting a somatic mutation in genes involved in DNA damage repair pathways and mismatch repair. The aim of the presented protocol is to identify germline pathogenic variants with prophylactic and therapeutic impact, and to collect and integrate a significant amount of clinical, familial, somatic, and genetic data.
- Published
- 2024
- Full Text
- View/download PDF
15. Unravelling Novel SCN5A Mutations Linked to Brugada Syndrome: Functional, Structural, and Genetic Insights.
- Author
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Frosio A, Micaglio E, Polsinelli I, Calamaio S, Melgari D, Prevostini R, Ghiroldi A, Binda A, Carrera P, Villa M, Mastrocinque F, Presi S, Salerno R, Boccellino A, Anastasia L, Ciconte G, Ricagno S, Pappone C, and Rivolta I
- Subjects
- Humans, NAV1.5 Voltage-Gated Sodium Channel genetics, Arrhythmias, Cardiac, Mutation, Brugada Syndrome genetics
- Abstract
Brugada Syndrome (BrS) is a rare inherited cardiac arrhythmia causing potentially fatal ventricular tachycardia or fibrillation, mainly occurring during rest or sleep in young individuals without heart structural issues. It increases the risk of sudden cardiac death, and its characteristic feature is an abnormal ST segment elevation on the ECG. While BrS has diverse genetic origins, a subset of cases can be conducted to mutations in the SCN5A gene, which encodes for the Nav1.5 sodium channel. Our study focused on three novel SCN5A mutations (p.A344S, p.N347K, and p.D349N) found in unrelated BrS families. Using patch clamp experiments, we found that these mutations disrupted sodium currents: p.A344S reduced current density, while p.N347K and p.D349N completely abolished it, leading to altered voltage dependence and inactivation kinetics when co-expressed with normal channels. We also explored the effects of mexiletine treatment, which can modulate ion channel function. Interestingly, the p.N347K and p.D349N mutations responded well to the treatment, rescuing the current density, while p.A344S showed a limited response. Structural analysis revealed these mutations were positioned in key regions of the channel, impacting its stability and function. This research deepens our understanding of BrS by uncovering the complex relationship between genetic mutations, ion channel behavior, and potential therapeutic interventions.
- Published
- 2023
- Full Text
- View/download PDF
16. APC -Related Phenotypes and Intellectual Disability in 5q Interstitial Deletions: A New Case and Review of the Literature.
- Author
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Privitera F, Piccini F, Recalcati MP, Presi S, Mazzola S, and Carrera P
- Subjects
- Humans, Chromosome Aberrations, Phenotype, Chromosome Deletion, Intellectual Disability genetics, Genes, APC, Adenomatous Polyposis Coli Protein genetics
- Abstract
The 5q deletion syndrome is a relatively rare condition caused by the monoallelic interstitial deletion of the long arm of chromosome 5. Patients described in literature usually present variable dysmorphic features, behavioral disturbance, and intellectual disability (ID); moreover, the involvement of the APC gene (5q22.2) in the deletion predisposes them to tumoral syndromes (Familial Adenomatous Polyposis and Gardner syndrome). Although the development of gastrointestinal tract malignancies has been extensively described, the genetic causes underlying neurologic manifestations have never been investigated. In this study, we described a new patient with a 19.85 Mb interstitial deletion identified by array-CGH and compared the deletions and the phenotypes reported in other patients already described in the literature and the Decipher database. Overlapping deletions allowed us to highlight a common region in 5q22.1q23.1, identifying KCNN2 (5q22.3) as the most likely candidate gene contributing to the neurologic phenotype.
- Published
- 2023
- Full Text
- View/download PDF
17. Novel JAG1 Deletion Variant in Patient with Atypical Alagille Syndrome.
- Author
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Micaglio E, Andronache AA, Carrera P, Monasky MM, Locati ET, Pirola B, Presi S, Carminati M, Ferrari M, Giamberti A, and Pappone C
- Subjects
- Alagille Syndrome blood, Alagille Syndrome diagnostic imaging, Base Sequence, Bilirubin blood, Electrocardiography, Female, Humans, Infant, Newborn, Male, Pedigree, Pulmonary Artery diagnostic imaging, Pulmonary Artery pathology, Alagille Syndrome genetics, Gene Deletion, Jagged-1 Protein genetics
- Abstract
Alagille syndrome (AGS) is an autosomal-dominant disorder characterized by various degrees of abnormalities in the liver, heart, eyes, vertebrae, kidneys, face, vasculature, skeleton, and pancreas. This case report describes a newborn child exhibiting a congenital neural tube defect and peculiar craniofacial appearance characterized by a prominent forehead, deep-set eyes, bulbous nasal tip, and subtle upper lip. Just a few hours after birth, congenital heart disease was suspected for cyanosis and confirmed by heart evaluation. In particular, echocardiography indicated pulmonary atresia with ventricular septal defect with severe hypoplasia of the pulmonary branches (1.5 mm), large patent ductus arteriosus and several major aortopulmonary collateral arteries. Due to the association of peculiar craniofacial appearance and congenital heart disease, a form of Alagille syndrome was suspected. In addition, on the fifth day after birth, the patient developed jaundice, had acholic stools, and high levels of conjugated bilirubin and gamma-glutamyltransferase (GGT) were detected in the blood. Genetic testing revealed the novel variant c.802del in a single copy of the JAG1 gene. No variants in the NOTCH2 gene were detected. To the best of our knowledge, this is the first clinical description of a congenital neural tube defect in a molecularly confirmed Alagille patient. This work demonstrates a novel pathogenic heterozygous JAG1 mutation is associated with an atypical form of Alagille syndrome, suggesting an increased risk for neural tube defects compared to other Alagille patients.
- Published
- 2019
- Full Text
- View/download PDF
18. Integration of multigene panels for the diagnosis of hereditary retinal disorders using Next Generation Sequencing and bioinformatics approaches.
- Author
-
Di Resta C, Spiga I, Presi S, Merella S, Pipitone GB, Manitto MP, Querques G, Parodi MB, Ferrari M, and Carrera P
- Abstract
In recent years, Next-Generation Sequencing (NGS) opened a new way for the study of pathogenic mechanisms and for molecular diagnosis of inherited disorders. In the present work, we focused our attention on the inherited retinal dystrophies (IRDs), a group of specific disorders of the retina, displaying a very high clinical and genetic heterogeneity, whose genetic diagnosis is not easily feasible. It represents a paradigmatic example for the integration of clinical and molecular examination toward precision medicine. In this paper, we discuss the use of targeted NGS resequencing of selected gene panels in a cohort of patients affected by IRDs. We tested the hypothesis to apply a selective approach based on a careful clinical examination. By this approach we reached a 66% overall detection rate for pathogenic variants, with a 52% diagnostic yield. Reduction of the efforts for validation and classification of variants is a clear advantage for the management of genetic testing in a clinical setting.
- Published
- 2018
19. Surfactant proteins gene variants in premature newborn infants with severe respiratory distress syndrome.
- Author
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Somaschini M, Presi S, Ferrari M, Vergani B, and Carrera P
- Subjects
- Female, Gene Expression Regulation genetics, Genetic Association Studies, Genetic Predisposition to Disease, Gestational Age, Heterozygote, Humans, Infant, Infant, Newborn, Infant, Premature, Italy, Lung ultrastructure, Male, Retrospective Studies, ATP-Binding Cassette Transporters genetics, Mutation, Pulmonary Surfactant-Associated Protein B genetics, Pulmonary Surfactant-Associated Protein C genetics, Respiratory Distress Syndrome, Newborn genetics
- Abstract
Objective: Genetic surfactant dysfunction causes respiratory failure in term and near-term newborn infants, but little is known of such condition in prematures. We evaluated genetic surfactant dysfunction in premature newborn infants with severe RDS., Patients and Methods: A total of 68 preterm newborn infants with gestational age ≤32 weeks affected by unusually severe RDS were analysed for mutations in SFTPB, SFTPC and ABCA3. Therapies included oxygen supplementation, nasal CPAP, different modalities of ventilatory support, administration of exogenous surfactant, inhaled nitric oxide and steroids. Molecular analyses were performed on genomic DNA extracted from peripheral blood and Sanger sequencing of whole gene coding regions and intron junctions. In one case histology and electron microscopy on lung tissue was performed., Results: Heterozygous previously described rare or novel variants in surfactant proteins genes ABCA3, SFTPB and SFTPC were identified in 24 newborn infants. In total, 11 infants died at age of 2 to 6 months. Ultrastructural analysis of lung tissue of one infant showed features suggesting ABCA3 dysfunction., Discussion: Rare or novel genetic variants in genes encoding surfactant proteins were identified in a large proportion (35%) of premature newborn infants with particularly severe RDS. We speculate that interaction of developmental immaturity of surfactant production in association with abnormalities of surfactant metabolism of genetic origin may have a synergic worsening phenotypic effect.
- Published
- 2018
- Full Text
- View/download PDF
20. Null ABCA3 in humans: large homozygous ABCA3 deletion, correlation to clinical-pathological findings.
- Author
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Carrera P, Ferrari M, Presi S, Ventura L, Vergani B, Lucchini V, Cogo PE, Carnielli VP, Somaschini M, and Tagliabue P
- Subjects
- ATP-Binding Cassette Transporters deficiency, Blotting, Southern, Fatal Outcome, Female, Homozygote, Humans, Infant, Newborn, Lung Diseases, Interstitial diagnosis, Lung Diseases, Interstitial genetics, Respiratory Distress Syndrome, Newborn diagnosis, Sequence Analysis, DNA, ATP-Binding Cassette Transporters genetics, Gene Deletion, Respiratory Distress Syndrome, Newborn genetics, Siblings
- Abstract
A study was undertaken to analyze the clinical presentation, pulmonary function, and pathological features in two female siblings with neonatal pulmonary surfactant metabolism dysfunction, type 3 (MIM 610921). The clinical records of the siblings were examined; the genes encoding surfactant protein B (SFTPB), surfactant protein C (SFTPC), and ATP-binding cassette transporter 3 protein (ABCA3) were analyzed with direct sequencing and Southern blotting. The infants were homozygous for a 5,983 bp deletion in ABCA3 including exons 2-5 as well as the start AUG codon and a putative Golgi exit signal motif. Dense abnormalities of lamellar bodies at electron microscopy and absence of ABCA3 at immunohistochemical staining were in agreement with the presence of two null alleles. In addition, an increased lipid synthesis suggested a compensatory mechanism. The clinical course in the two sisters was influenced by different environmental factors like the time needed for molecular confirmation, the ventilatory assistance adopted, the occurrence of infections. A less aggressive clinical approach did not improve the course of the disease; the prognosis was always poor. Development of a fast molecular test, able to detect also structural variants, is needed., (© 2014 Wiley Periodicals, Inc.)
- Published
- 2014
- Full Text
- View/download PDF
21. Genetic susceptibility to neonatal lung diseases.
- Author
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Somaschini M, Castiglioni E, Presi S, Volonteri C, Ferrari M, and Carrera P
- Subjects
- ATP-Binding Cassette Transporters genetics, Bronchopulmonary Dysplasia epidemiology, Genetic Predisposition to Disease epidemiology, Glutathione S-Transferase pi genetics, Humans, Infant, Newborn, Matrix Metalloproteinase 16 genetics, Peptidyl-Dipeptidase A genetics, Proteoglycans genetics, Pulmonary Surfactant-Associated Protein B genetics, Pulmonary Surfactant-Associated Protein C genetics, Respiratory Distress Syndrome, Newborn epidemiology, Risk Factors, Toll-Like Receptor 5 genetics, Tumor Necrosis Factor-alpha genetics, Vascular Endothelial Growth Factor A genetics, Bronchopulmonary Dysplasia genetics, Genetic Predisposition to Disease genetics, Respiratory Distress Syndrome, Newborn genetics
- Abstract
Advances in molecular genetics have enabled improvement of knowledge in pathogenesis and diagnosis of either monogenic or multifactorial neonatal lung diseases. Variants in genes regulating surfactant function and metabolism are implicated in some rare and common respiratory diseases. Congenital surfactant deficiencies are rare diseases due to mutations in genes encoding surfactant proteins and cause significant and often lethal respiratory failure in newborns and interstitial lung disease in older children. Diagnosis is made by molecular analysis and eventually confirmed by histological analysis of lung tissue. A multifactorial contribution, resulting from interaction between multiple genes and environmental factors, has been supposed for respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD). Several potential candidate genes, especially regarding surfactant proteins and cytokines, have been shown in association with these diseases. Genetic variants predisposing to RDS or BPD are usually polymorphisms which are not causative, but can increase susceptibility to the disease. Identification of infants at risk of disease can be useful to provide them individualized therapies. (www.actabiomedica.it).
- Published
- 2012
22. Unexplained neonatal respiratory distress due to congenital surfactant deficiency.
- Author
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Somaschini M, Nogee LM, Sassi I, Danhaive O, Presi S, Boldrini R, Montrasio C, Ferrari M, Wert SE, and Carrera P
- Subjects
- Birth Weight, Female, Gestational Age, Humans, Immunohistochemistry, Infant, Newborn, Lung diagnostic imaging, Male, Mutation, Missense, Phenotype, Pulmonary Surfactant-Associated Protein B metabolism, Ultrasonography, ATP-Binding Cassette Transporters genetics, Pulmonary Surfactant-Associated Protein B genetics, Pulmonary Surfactant-Associated Protein C genetics, Pulmonary Surfactants, Respiratory Distress Syndrome, Newborn genetics, Sequence Analysis, DNA
- Abstract
Genetic abnormalities of pulmonary surfactant were identified by DNA sequence analysis in 14 (12 full-term, 2 preterm) of 17 newborn infants with fatal respiratory distress of unknown etiology. Deficiency of adenosine triphosphate-binding cassette protein, member A3 (n = 12) was a more frequent cause of this phenotype than deficiency of surfactant protein B (n = 2).
- Published
- 2007
- Full Text
- View/download PDF
23. Phylogenetic internal control for HIV-1 genotypic antiretroviral testing.
- Author
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Boeri E, Canducci F, Grasso MA, Presi S, Carrera P, Racca S, and Clementi M
- Subjects
- Amino Acid Sequence, Base Sequence, Drug Resistance, Viral, Genotype, HIV Protease genetics, HIV Reverse Transcriptase genetics, HIV-1 classification, HIV-1 isolation & purification, Humans, Microbial Sensitivity Tests, Quality Control, Sequence Homology, Anti-HIV Agents pharmacology, HIV Infections virology, HIV-1 drug effects, HIV-1 genetics, Phylogeny
- Abstract
Genotypic testing includes several steps (RNA purification, RT-PCR amplification, DNA sequencing, sequence editing and analysis) that should be individually controlled. In our laboratory, we have added to this step-by-step internal control a final phylogenetic quality control: this is performed every time a sequence is obtained from a patient previously subjected to the same test. Each sequence with this characteristic is routinely compared with sequences from previous samples of the same patient by multiple alignment and a neighbor-joining tree by using Kimura two-parameter method is constructed. To validate the quality control procedure, we have aligned and calculated the mean similarity of the reverse transcriptase (first 984 nucleotides) and protease (whole gene) sequences from 30 patients whose virus was completely wild-type for both reverse transcriptase and protease. In the same tree, we have added the sequences obtained from 5 out of the 30 patients, tested at a second time point. The wild type sequences have shown a mean inter-sample divergence of 2.9%, and all the sequence pairs from individual patients clustered together in the tree constructed with the nucleotide sequences, while the tree constructed with the inferred aminoacid sequences did not always permit to cluster the sequences from the same patients. This indicates that: 1) the phylogenetic analysis of nucleic acid sequences can be useful to rule out sample mix-up; 2) the belonging of a sequence to each individual patient can efficiently be assessed also in the cases of extreme divergence in terms of drug resistance mutations.
- Published
- 2004
24. Long-term virological effect of highly active antiretroviral therapy on cerebrospinal fluid and relationship with genotypic resistance.
- Author
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Bestetti A, Presi S, Pierotti C, Bossolasco S, Sala S, Racca S, Carrera P, Lazzarin A, and Cinque P
- Subjects
- AIDS Dementia Complex cerebrospinal fluid, AIDS Dementia Complex virology, Drug Resistance, Viral genetics, Follow-Up Studies, Genotype, HIV Protease Inhibitors therapeutic use, Humans, Mutation, RNA, Viral blood, RNA, Viral cerebrospinal fluid, Reverse Transcriptase Inhibitors therapeutic use, Viral Load, AIDS Dementia Complex drug therapy, Antiretroviral Therapy, Highly Active, HIV-1 drug effects, HIV-1 genetics
- Abstract
The objective of this study was to assess the long-term virological response in cerebrospinal fluid (CSF) in patients treated with highly active antiretroviral therapy (HAART) and to compare this response to CSF and plasma human immunodeficiency virus (HIV) drug resistance profiles. Paired CSF and plasma specimens were drawn from 18 patients receiving HAART at baseline and after 9 to 70 months of therapy. At baseline, median HIV-1 RNA concentrations were 4.13 log10 copies/ml in CSF and 5.31 log10 copies/ml in plasma. At the time of on-therapy CSF sampling, HIV-1 RNA was undetectable in CSF from 13/18 patients (72%), and in plasma from 9/18 patients (50%). The genotypic analysis at baseline revealed reverse transcriptase (RT) resistance mutations in 7 of 11 (64%) CSF samples and in 8 of 11 (73%) plasma samples. No patient had protease resistance mutations, except for secondary mutations. At the time of virological failure in CSF, new RT and protease resistance mutations were found in both CSF and plasma of the two patients with both baseline and on-treatment paired evaluations. At long-term follow-up, the proportion of patients failing to respond virologically was lower in CSF than in plasma. Virological failure in CSF was associated with failure to respond in plasma and onset of new drug resistance mutations in both compartments.
- Published
- 2004
- Full Text
- View/download PDF
25. Effect of genotypic resistance on the virological response to highly active antiretroviral therapy in cerebrospinal fluid.
- Author
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Cinque P, Presi S, Bestetti A, Pierotti C, Racca S, Boeri E, Morelli P, Carrera P, Ferrari M, and Lazzarin A
- Subjects
- Adult, Antiretroviral Therapy, Highly Active, Base Sequence, Central Nervous System Viral Diseases virology, Female, Follow-Up Studies, Genotype, HIV Infections blood, HIV Infections cerebrospinal fluid, HIV Infections drug therapy, HIV Reverse Transcriptase drug effects, Humans, Male, Middle Aged, Molecular Sequence Data, Mutation, Predictive Value of Tests, Sequence Alignment, Viral Load, Viremia drug therapy, Cerebrospinal Fluid virology, Drug Resistance, Microbial genetics, Drug Resistance, Multiple genetics, HIV Infections virology, HIV Protease genetics, HIV Reverse Transcriptase genetics, HIV-1 drug effects, HIV-1 genetics
- Abstract
Paired plasma and cerebrospinal fluid (CSF) specimens drawn from 15 HIV-infected patients with neurological disease before and after a median 6-week duration of highly active antiretroviral therapy (HAART) were studied to assess the short-term virological response of CSF and whether this can be predicted on the basis of baseline resistance mutations. After treatment, the median plasma and CSF viral load (VL) decreased by, respectively, 2.08 log10 (p = 0.0001) and 0.91 log10 copies/ml (p = 0.007) in comparison with baseline. A plasma virological response was observed in all but one patient, whereas the posttreatment CSF VL increased, remained unchanged, or decreased at a substantial lower rate than in plasma of six "CSF non/slow responders" (40%). Direct sequencing of baseline specimens showed that none of these patients had reverse transcriptase (RT) or primary protease resistance mutations in the CSF alone, but two had RT mutations conferring high-level resistance to drugs included in the HAART regimen in both CSF and plasma. The other four patients had no RT or primary protease resistance mutations. There was no significant difference in the nucleotide diversity of the CSF and plasma RT sequences, baseline plasma or CSF VL, the CSF-to-plasma VL ratio, the number of CSF cells, the CD4+ cell counts, or the history of antiretroviral treatment between the CSF non-slow responders and the other patients. During this short-term follow-up and despite a plasma response, a significant proportion of HAART-treated patients with neurological symptoms showed a slow or absent CSF response. Most of these cases were not associated with the presence of resistant HIV strains in the CSF.
- Published
- 2001
- Full Text
- View/download PDF
26. Molecular analysis of cerebrospinal fluid: potential for the study of HIV-1 infection of the central nervous system.
- Author
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Cinque P, Bestetti A, Morelli P, and Presi S
- Subjects
- Anti-HIV Agents cerebrospinal fluid, Anti-HIV Agents therapeutic use, Drug Resistance, Microbial, Humans, RNA, Viral cerebrospinal fluid, Viral Load, Central Nervous System virology, HIV Infections cerebrospinal fluid, HIV-1 pathogenicity
- Abstract
The molecular analysis of cerebrospinal fluid (CSF) provides an inestimable tool for the study of HIV infection of the central nervous system (CNS). Current nucleic acid amplification techniques enable the measurement of CSF HIV-1 RNA levels which can be predictive of HIV-associated neurological damage. CSF HIV-1 RNA levels do not necessarily correlate with the corresponding plasma levels, thus supporting the possibility of an intrathecal virus production, i.e., from brain macrophages. However, in early stages of HIV infection, as well as during some opportunistic CNS diseases, CNS or CSF infiltrating lymphocytes might be the main source of CSF virus. A drastic decrease in CSF viral load is usually observed along with a decrease in plasma levels in patients receiving highly active antiretroviral therapy (HAART), with durable suppression of CSF viral load over months. However, during the first weeks of therapy, the dynamics of response may differ in the CSF as compared to plasma, again suggesting that virus replication may be compartmentalised in the CSF. A number of mechanisms are likely to be involved in the response to therapy in CSF, including among the others the trafficking of cell populations supporting viral replication between blood, CNS and CSF, and the role of the anatomical brain barriers in limiting the access of antiretroviral drugs into the CSF. A potential risk associated with compartmentalisation of HIV infection is of an incomplete suppression of virus replication in the CSF, thus creating the ground for local development of anti-HIV drug resistance. In order to assess this occurrence, long-term studies of viral load and genotypic analyses on paired CSF and plasma will be necessary and these will also help elucidate the complex interrelationship between viral replication in these compartments.
- Published
- 2000
27. Study on mutations and antiretroviral therapy (SMART): preliminary results.
- Author
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Gianotti N, Moretti F, Tambussi G, Racca S, Presi S, Crucianelli R, Carrera P, Ferrari M, and Lazzarin A
- Subjects
- Anti-HIV Agents administration & dosage, Anti-HIV Agents therapeutic use, Drug Therapy, Combination, HIV Infections virology, HIV-1 drug effects, HIV-1 genetics, Humans, Italy, Microbial Sensitivity Tests, Phenotype, RNA, Viral blood, Reverse Transcriptase Inhibitors administration & dosage, Reverse Transcriptase Inhibitors therapeutic use, Anti-HIV Agents pharmacology, Drug Resistance, Viral genetics, HIV Infections drug therapy, Mutation, Reverse Transcriptase Inhibitors pharmacology
- Abstract
Resistance to antiretroviral drugs is believed to be an important cause of treatment failure in human immunodeficiency virus (HIV)-infected patients, however, the role of susceptibility assays in the management of these individuals needs to be defined. SMART (study on mutations and antiretroviral therapy) is an ongoing study on mutations and antiretroviral therapy focused particularly on HIV-infected patients treated with two nucleoside analogue reverse transcriptase inhibitors (NRTIs). Plasma HIV-1 RNA was assessed by NASBA (nucleic acid sequence-based amplifications) (Organon Teknika, Boxtel, The Netherlands) with a detection limit of 80 copies/ml, whereas resistance was assessed by direct sequencing of the RT pol gene in patients with detectable viraemia, and by Antivirogram (Virco) in non-responder patients. The preliminary results of this study show that both genotypic and phenotypic assays identify mutated viral strains in the majority of patients failing a dual regimen. Furthermore, the data indicate a high rate of genotypic resistance to lamivudine in both responders and non-responders, a high rate of phenotypic resistance to lamivudine in non-responders, no genotypic resistance to didanosine and stavudine in responders, and a very low rate of both genotypic and phenotypic resistance to didanosine and stavudine in non-responders.
- Published
- 1999
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