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1. Pathogenic cryptic variants detectable through exome data reanalysis significantly increase the diagnostic yield in Joubert syndrome

Author

D’Abrusco, Fulvio, Serpieri, Valentina, Taccagni, Cecilia Maria, Garau, Jessica, Cattaneo, Luca, Boggioni, Monica, Gana, Simone, Battini, Roberta, Bertini, Enrico, Zanni, Ginevra, Boltshauser, Eugen, Borgatti, Renato, Romaniello, Romina, Signorini, Sabrina, Leuzzi, Vincenzo, Caputi, Caterina, Manti, Filippo, D’Arrigo, Stefano, De Laurentiis, Arianna, Graziano, Claudio, Lemke, Johannes R., Morelli, Federica, Petković Ramadža, Danijela, Sirchia, Fabio, Giorgio, Elisa, and Valente, Enza Maria

Published
2025
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2. Expanding the Phenotypic Spectrum of GPI Anchoring Deficiency Due to Biallelic Variants in GPAA1.

Author

Heron, Delphine, Keren, Boris, Johnstone, Devon, Mears, Wendy, Morlot, Susanne, Nguyen, Thi, Rock, Rachel, Stolerman, Elliot, Russo, Julia, Burns, William, Jones, Julie, Serpieri, Valentina, Wallaschek, Hannah, Zanni, Ginevra, Dyment, David, Campeau, Philippe, Castle, Alison, Salian, Smrithi, Bassan, Haim, Sofrin-Drucker, Efrat, Cusmai, Raffaella, and Herman, Kristin

Abstract

BACKGROUND AND OBJECTIVES: To expand the clinical knowledge of GPAA1-related glycosylphosphatidylinositol (GPI) deficiency. METHODS: An international case series of 7 patients with biallelic GPAA1 variants were identified. Clinical, biochemical, and neuroimaging data were collected for comparison. Where possible, GPI-anchored proteins were assessed using flow cytometry. RESULTS: Ten novel variants were identified in 7 patients. Flow cytometry samples of 3 available patients confirmed deficiency of several GPI-anchored proteins on leukocytes. Extensive phenotypic information was available for each patient. The majority experienced developmental delay, seizures, and hypotonia. Neuroimaging revealed cerebellar anomalies in the majority of the patients. Alkaline phosphatase was within the normal range in 5 individuals and low in 1 individual, as has been noted in other transamidase defects. We notably describe individuals either less affected or older than the ones published previously. DISCUSSION: Clinical features of the cases reported broaden the spectrum of the known phenotype of GPAA1-related GPI deficiency, while outlining the importance of using functional studies such as flow cytometry to aid in variant classification.

Published
2021

7. Expanding the Phenotypic Spectrum of GPI Anchoring Deficiency Due to Biallelic Variants in GPAA1

Author

Castle, Alison M.R., Salian, Smrithi, Bassan, Haim, Sofrin-Drucker, Efrat, Cusmai, Raffaella, Herman, Kristin C., Heron, Delphine, Keren, Boris, Johnstone, Devon L., Mears, Wendy, Morlot, Susanne, Nguyen, Thi Tuyet Mai, Rock, Rachel, Stolerman, Elliot, Russo, Julia, Burns, William Boyce, Jones, Julie R., Serpieri, Valentina, Wallaschek, Hannah, Zanni, Ginevra, Dyment, David A., and Campeau, Philippe M.

Published
2021
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9. Visual function in children with Joubert syndrome.

Author

Morelli, Federica, Toni, Federico, Saligari, Elena, D'Abrusco, Fulvio, Serpieri, Valentina, Ballante, Elena, Ruberto, Giulio, Borgatti, Renato, Valente, Enza Maria, Signorini, Sabrina, Bertone, Chiara, Misefari, Walter, Antonini, Mauro, Paini, Daria, Perotto, Eleonora, Luparia, Antonella, Olivier, Lucrezia, Ercolino, Elisa, and Pichiecchio, Anna

Subjects
JOUBERT syndrome, VISION, SYNDROMES in children, VISUAL acuity, RETINAL degeneration
Abstract

Aim: To describe visual function in children with Joubert syndrome and to investigate its possible association with diagnostic and developmental aspects. Method: This retrospective cross‐sectional work included 59 patients (33 male; mean age 9 years 2 months, standard deviation 6 years 3 months, range 4 months to 23 years) diagnosed with Joubert syndrome from January 2002 to December 2020. Data about clinical (neurological, neuro‐ophthalmological, developmental/cognitive) and diagnostic (e.g. genetic testing, neuroimaging, systemic involvement) evaluations were collected in a data set during a review of medical records. Clinical and diagnostic variables were described in terms of raw counts and percentages. A χ2 test was conducted to investigate their association with neuropsychological skills. Results: Ocular motor apraxia was highly represented in our cohort (75%), with a high prevalence of refractive defects and retinal abnormalities. Developmental delay/intellectual disability was frequent (in 69.5% of the sample), associated with retinal dystrophy (p = 0.047) and reduced visual acuity both for near (p = 0.014) and for far distances (p = 0.017). Interpretation: On the basis of the relevance of oculomotor and perceptual alterations and their impact on overall and cognitive impairment, we encourage early and multidisciplinary assessment and follow‐up of visual function in children with Joubert syndrome. This would help in planning a personalized rehabilitation to sustain functional vision. Further studies will be important to explore the link between biological aspects and global functioning in children with Joubert syndrome. What this paper adds: Perceptual deficits and oculomotor impairments frequently coexist in Joubert syndrome.Retinal dysfunction may be present despite the absence of funduscopic abnormalities.Both perceptual and oculomotor impairments negatively affect cognitive development in Joubert syndrome. What this paper adds: Perceptual deficits and oculomotor impairments frequently coexist in Joubert syndrome.Retinal dysfunction may be present despite the absence of funduscopic abnormalities.Both perceptual and oculomotor impairments negatively affect cognitive development in Joubert syndrome. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Recurrent, founder and hypomorphic variants contribute to the genetic landscape of Joubert syndrome

Author

Serpieri, Valentina, primary, Mortarini, Giulia, additional, Loucks, Hailey, additional, Biagini, Tommaso, additional, Micalizzi, Alessia, additional, Palmieri, Ilaria, additional, Dempsey, Jennifer C, additional, D’Abrusco, Fulvio, additional, Mazzotta, Concetta, additional, Battini, Roberta, additional, Bertini, Enrico Silvio, additional, Boltshauser, Eugen, additional, Borgatti, Renato, additional, Brockmann, Knut, additional, D'Arrigo, Stefano, additional, Nardocci, Nardo, additional, Fischetto, Rita, additional, Agolini, Emanuele, additional, Novelli, Antonio, additional, Romano, Alfonso, additional, Romaniello, Romina, additional, Stanzial, Franco, additional, Signorini, Sabrina, additional, Strisciuglio, Pietro, additional, Gana, Simone, additional, Mazza, Tommaso, additional, Doherty, Dan, additional, and Valente, Enza Maria, additional

Published
2023
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14. Superior Cerebellar Atrophy: An Imaging Clue to Diagnose ITPR1-Related Disorders

Author

Romaniello, Romina, primary, Pasca, Ludovica, additional, Panzeri, Elena, additional, D’Abrusco, Fulvio, additional, Travaglini, Lorena, additional, Serpieri, Valentina, additional, Signorini, Sabrina, additional, Aiello, Chiara, additional, Bertini, Enrico, additional, Bassi, Maria Teresa, additional, Valente, Enza Maria, additional, Zanni, Ginevra, additional, Borgatti, Renato, additional, and Arrigoni, Filippo, additional

Published
2022
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16. Get Your Molar Tooth Right: Joubert Syndrome Misdiagnosis Unmasked by Whole-Exome Sequencing.

Author

D'Abrusco, Fulvio, Arrigoni, Filippo, Serpieri, Valentina, Romaniello, Romina, Caputi, Caterina, Manti, Filippo, Jocic-Jakubi, Bosanka, Lucarelli, Elisabetta, Panzeri, Elena, Bonaglia, Maria Clara, Chiapparini, Luisa, Pichiecchio, Anna, Pinelli, Lorenzo, Righini, Andrea, Leuzzi, Vincenzo, Borgatti, Renato, and Valente, Enza Maria

Subjects
JOUBERT syndrome, GENETIC testing, GENETIC disorder diagnosis, SYMPTOMS, OLDER patients, OCULAR hypotony, SPEECH apraxia
Abstract

Joubert syndrome (JS) is a recessively inherited ciliopathy, characterized by a specific cerebellar and brainstem malformation recognizable on brain imaging as the "molar tooth sign" (MTS). Clinical signs include hypotonia, developmental delay, breathing abnormalities, and ocular motor apraxia. Older patients develop ataxia, intellectual impairment, and variable organ involvement. JS is genetically heterogeneous, with over 40 ciliary genes overall accounting for 65–75% cases. Thus, in recent years, the genetic diagnosis of JS has been based on the analysis of next-generation sequencing targeted gene panels. Since clinical features are unspecific and undistinguishable from other neurodevelopmental syndromes, the recognition of the MTS is crucial to address the patient to the appropriate genetic testing. However, the MTS is not always properly diagnosed, resulting either in false negative diagnoses (patients with the MTS not addressed to JS genetic testing) or in false positive diagnoses (patients with a different brain malformation wrongly addressed to JS genetic testing). Here, we present six cases referred for JS genetic testing based on inappropriate recognition of MTS. While the analysis of JS-related genes was negative, whole-exome sequencing (WES) disclosed pathogenic variants in other genes causative of distinct brain malformative conditions with partial clinical and neuroradiological overlap with JS. Reassessment of brain MRIs from five patients by a panel of expert pediatric neuroradiologists blinded to the genetic diagnosis excluded the MTS in all cases but one, which raised conflicting interpretations. This study highlights that the diagnostic yield of NGS-based targeted panels is strictly related to the accuracy of the diagnostic referral based on clinical and imaging assessment and that WES has an advantage over targeted panel analysis when the diagnostic suspicion is not straightforward. [ABSTRACT FROM AUTHOR]

Published
2022
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17. Get Your Molar Tooth Right: Joubert Syndrome Misdiagnosis Unmasked by Whole-Exome Sequencing

Author

D’Abrusco, Fulvio, primary, Arrigoni, Filippo, additional, Serpieri, Valentina, additional, Romaniello, Romina, additional, Caputi, Caterina, additional, Manti, Filippo, additional, Jocic-Jakubi, Bosanka, additional, Lucarelli, Elisabetta, additional, Panzeri, Elena, additional, Bonaglia, Maria Clara, additional, Chiapparini, Luisa, additional, Pichiecchio, Anna, additional, Pinelli, Lorenzo, additional, Righini, Andrea, additional, Leuzzi, Vincenzo, additional, Borgatti, Renato, additional, and Valente, Enza Maria, additional

Published
2021
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18. SUFU haploinsufficiency causes a recognisable neurodevelopmental phenotype at the mild end of the Joubert syndrome spectrum

Author

Serpieri, Valentina, primary, D’Abrusco, Fulvio, additional, Dempsey, Jennifer C, additional, Cheng, Yong-Han Hank, additional, Arrigoni, Filippo, additional, Baker, Janice, additional, Battini, Roberta, additional, Bertini, Enrico Silvio, additional, Borgatti, Renato, additional, Christman, Angela K, additional, Curry, Cynthia, additional, D'Arrigo, Stefano, additional, Fluss, Joel, additional, Freilinger, Michael, additional, Gana, Simone, additional, Ishak, Gisele E, additional, Leuzzi, Vincenzo, additional, Loucks, Hailey, additional, Manti, Filippo, additional, Mendelsohn, Nancy, additional, Merlini, Laura, additional, Miller, Caitlin V, additional, Muhammad, Ansar, additional, Nuovo, Sara, additional, Romaniello, Romina, additional, Schmidt, Wolfgang, additional, Signorini, Sabrina, additional, Siliquini, Sabrina, additional, Szczałuba, Krzysztof, additional, Vasco, Gessica, additional, Wilson, Meredith, additional, Zanni, Ginevra, additional, Boltshauser, Eugen, additional, Doherty, Dan, additional, and Valente, Enza Maria, additional

Published
2021
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19. SUFU haploinsufficiency causes a recognisable neurodevelopmental phenotype at the mild end of the Joubert syndrome spectrum.

Author

Serpieri, Valentina, D’Abrusco, Fulvio, Dempsey, Jennifer C., Yong-Han Hank Cheng, Arrigoni, Filippo, Baker, Janice, Battini, Roberta, Bertini, Enrico Silvio, Borgatti, Renato, Christman, Angela K., Curry, Cynthia, D’Arrigo, Stefano, Fluss, Joel, Freilinger, Michael, Gana, Simone, Ishak, Gisele E., Leuzzi, Vincenzo, Loucks, Hailey, Manti, Filippo, and Mendelsohn, Nancy

Abstract

Background Joubert syndrome (JS) is a recessively inherited ciliopathy characterised by congenital ocular motor apraxia (COMA), developmental delay (DD), intellectual disability, ataxia, multiorgan involvement, and a unique cerebellar and brainstem malformation. Over 40 JS-associated genes are known with a diagnostic yield of 60%–75%. In 2018, we reported homozygous hypomorphic missense variants of the SUFU gene in two families with mild JS. Recently, heterozygous truncating SUFU variants were identified in families with dominantly inherited COMA, occasionally associated with mild DD and subtle cerebellar anomalies. Methods We reanalysed next generation sequencing (NGS) data in two cohorts comprising 1097 probands referred for genetic testing of JS genes. Results Heterozygous truncating and splice-site SUFU variants were detected in 22 patients from 17 families (1.5%) with strong male prevalence (86%), and in 8 asymptomatic parents. Patients presented with COMA, hypotonia, ataxia and mild DD, and only a third manifested intellectual disability of variable severity. Brain MRI showed consistent findings characterised by vermis hypoplasia, superior cerebellar dysplasia and subtle-to-mild abnormalities of the superior cerebellar peduncles. The same pattern was observed in two out of three tested asymptomatic parents. Conclusion Heterozygous truncating or splice-site SUFU variants cause a novel neurodevelopmental syndrome encompassing COMA and mild JS, which likely represent overlapping entities. Variants can arise de novo or be inherited from a healthy parent, representing the first cause of JS with dominant inheritance and reduced penetrance. Awareness of this condition will increase the diagnostic yield of JS genetic testing, and allow appropriate counselling about prognosis, medical monitoring and recurrence risk. [ABSTRACT FROM AUTHOR]

Published
2022
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20. Refining the mutational spectrum and gene–phenotype correlates in pontocerebellar hypoplasia: results of a multicentric study

Author

Nuovo, Sara, primary, Micalizzi, Alessia, additional, Romaniello, Romina, additional, Arrigoni, Filippo, additional, Ginevrino, Monia, additional, Casella, Antonella, additional, Serpieri, Valentina, additional, D'Arrigo, Stefano, additional, Briguglio, Marilena, additional, Salerno, Grazia Gabriella, additional, Rossato, Sara, additional, Sartori, Stefano, additional, Leuzzi, Vincenzo, additional, Battini, Roberta, additional, Ben-Zeev, Bruria, additional, Graziano, Claudio, additional, Mirabelli Badenier, Marisol, additional, Brankovic, Vesna, additional, Nardocci, Nardo, additional, Spiegel, Ronen, additional, Petković Ramadža, Danijela, additional, Vento, Giovanni, additional, Marti, Itxaso, additional, Simonati, Alessandro, additional, Dipresa, Savina, additional, Freri, Elena, additional, Mazza, Tommaso, additional, Bassi, Maria Teresa, additional, Bosco, Luca, additional, Travaglini, Lorena, additional, Zanni, Ginevra, additional, Bertini, Enrico Silvio, additional, Vanacore, Nicola, additional, Borgatti, Renato, additional, and Valente, Enza Maria, additional

Published
2021
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22. Generation of induced pluripotent stem cell (iPSC) lines from a Joubert syndrome patient with compound heterozygous mutations in C5orf42 gene

Author

Ali, Eltahir, primary, Ferraro, Rosalba Monica, additional, Lanzi, Gaetana, additional, Masneri, Stefania, additional, Piovani, Giovanna, additional, Mazzoldi, Elena Laura, additional, Serpieri, Valentina, additional, Valente, Enza Maria, additional, Giordano, Lucio, additional, and Giliani, Silvia Clara, additional

Published
2020
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23. Visual Evoked Potentials in Joubert Syndrome: A Suggested Useful Method for Evaluating Future Approaches Targeted to Improve Visual Pathways’ Function

Author

Ruberto, Giulio, primary, Parisi, Vincenzo, additional, Bertone, Chiara, additional, Signorini, Sabrina, additional, Antonini, Mauro, additional, Valente, Enza Maria, additional, Manzoni, Federica, additional, Serpieri, Valentina, additional, Fausto, Riccardo, additional, and Quaranta, Luciano, additional

Published
2020
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25. Refining the mutational spectrum and gene–phenotype correlates in pontocerebellar hypoplasia: results of a multicentric study

Author

Nuovo, Sara, Micalizzi, Alessia, Romaniello, Romina, Arrigoni, Filippo, Ginevrino, Monia, Casella, Antonella, Serpieri, Valentina, D'Arrigo, Stefano, Briguglio, Marilena, Salerno, Grazia Gabriella, Rossato, Sara, Sartori, Stefano, Leuzzi, Vincenzo, Battini, Roberta, Ben-Zeev, Bruria, Graziano, Claudio, Mirabelli Badenier, Marisol, Brankovic, Vesna, Nardocci, Nardo, Spiegel, Ronen, Petković Ramadža, Danijela, Vento, Giovanni, Marti, Itxaso, Simonati, Alessandro, Dipresa, Savina, Freri, Elena, Mazza, Tommaso, Bassi, Maria Teresa, Bosco, Luca, Travaglini, Lorena, Zanni, Ginevra, Bertini, Enrico Silvio, Vanacore, Nicola, Borgatti, Renato, and Valente, Enza Maria

Abstract

BackgroundPontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorders characterised by concurrent hypoplasia of the pons and the cerebellum and variable clinical and imaging features. The current classification includes 13 subtypes, with ~20 known causative genes. Attempts have been made to delineate the phenotypic spectrum associated to specific PCH genes, yet clinical and neuroradiological features are not consistent across studies, making it difficult to define gene-specific outcomes.MethodsWe performed deep clinical and imaging phenotyping in 56 probands with a neuroradiological diagnosis of PCH, who underwent NGS-based panel sequencing of PCH genes and MLPA for CASKrearrangements. Next, we conducted a phenotype-based unsupervised hierarchical cluster analysis to investigate associations between genes and specific phenotypic clusters.ResultsA genetic diagnosis was obtained in 43 probands (77%). The most common causative gene was CASK, which accounted for nearly half cases (45%) and was mutated in females and occasionally in males. The European founder mutation p.Ala307Ser in TSEN54and pathogenic variants in EXOSC3accounted for 18% and 9% of cases, respectively. VLDLR, TOE1and RARS2were mutated in single patients. We were able to confirm only few previously reported associations, including jitteriness and clonus with TSEN54and lower motor neuron signs with EXOSC3. When considering multiple features simultaneously, a clear association with a phenotypic cluster only emerged for EXOSC3.ConclusionCASKrepresents the major PCH causative gene in Italy. Phenotypic variability associated with the most common genetic causes of PCH is wider than previously thought, with marked overlap between CASKand TSEN54-associated disorders.

Published
2022
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26. SUFUhaploinsufficiency causes a recognisable neurodevelopmental phenotype at the mild end of the Joubert syndrome spectrum

Author

Serpieri, Valentina, D’Abrusco, Fulvio, Dempsey, Jennifer C, Cheng, Yong-Han Hank, Arrigoni, Filippo, Baker, Janice, Battini, Roberta, Bertini, Enrico Silvio, Borgatti, Renato, Christman, Angela K, Curry, Cynthia, D'Arrigo, Stefano, Fluss, Joel, Freilinger, Michael, Gana, Simone, Ishak, Gisele E, Leuzzi, Vincenzo, Loucks, Hailey, Manti, Filippo, Mendelsohn, Nancy, Merlini, Laura, Miller, Caitlin V, Muhammad, Ansar, Nuovo, Sara, Romaniello, Romina, Schmidt, Wolfgang, Signorini, Sabrina, Siliquini, Sabrina, Szczałuba, Krzysztof, Vasco, Gessica, Wilson, Meredith, Zanni, Ginevra, Boltshauser, Eugen, Doherty, Dan, and Valente, Enza Maria

Abstract

BackgroundJoubert syndrome (JS) is a recessively inherited ciliopathy characterised by congenital ocular motor apraxia (COMA), developmental delay (DD), intellectual disability, ataxia, multiorgan involvement, and a unique cerebellar and brainstem malformation. Over 40 JS-associated genes are known with a diagnostic yield of 60%–75%.In 2018, we reported homozygous hypomorphic missense variants of the SUFUgene in two families with mild JS. Recently, heterozygous truncating SUFUvariants were identified in families with dominantly inherited COMA, occasionally associated with mild DD and subtle cerebellar anomalies.MethodsWe reanalysed next generation sequencing (NGS) data in two cohorts comprising 1097 probands referred for genetic testing of JS genes.ResultsHeterozygous truncating and splice-site SUFUvariants were detected in 22 patients from 17 families (1.5%) with strong male prevalence (86%), and in 8 asymptomatic parents. Patients presented with COMA, hypotonia, ataxia and mild DD, and only a third manifested intellectual disability of variable severity. Brain MRI showed consistent findings characterised by vermis hypoplasia, superior cerebellar dysplasia and subtle-to-mild abnormalities of the superior cerebellar peduncles. The same pattern was observed in two out of three tested asymptomatic parents.ConclusionHeterozygous truncating or splice-site SUFUvariants cause a novel neurodevelopmental syndrome encompassing COMA and mild JS, which likely represent overlapping entities. Variants can arise de novo or be inherited from a healthy parent, representing the first cause of JS with dominant inheritance and reduced penetrance. Awareness of this condition will increase the diagnostic yield of JS genetic testing, and allow appropriate counselling about prognosis, medical monitoring and recurrence risk.

Published
2022
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27. Human trisomy 21 fibroblasts rescue methotrexate toxic effect after treatment with 5‐methyl‐tetrahydrofolate and 5‐formyl‐tetrahydrofolate

Author

Vitale, Lorenza, primary, Serpieri, Valentina, additional, Lauriola, Mattia, additional, Piovesan, Allison, additional, Antonaros, Francesca, additional, Cicchini, Elena, additional, Locatelli, Chiara, additional, Cocchi, Guido, additional, Strippoli, Pierluigi, additional, and Caracausi, Maria, additional

Published
2019
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28. Human trisomy 21 fibroblasts rescue methotrexate toxic effect after treatment with 5-methyl-tetrahydrofolate and 5-formyl-tetrahydrofolate

Author

Valentina Serpieri, Lorenza Vitale, Guido Cocchi, Allison Piovesan, Francesca Antonaros, Mattia Lauriola, Chiara Locatelli, Pierluigi Strippoli, Elena Cicchini, Maria Caracausi, Vitale, Lorenza, Serpieri, Valentina, Lauriola, Mattia, Piovesan, Allison, Antonaros, Francesca, Cicchini, Elena, Locatelli, Chiara, Cocchi, Guido, Strippoli, Pierluigi, and Caracausi, Maria

Subjects
0301 basic medicine, Down syndrome, Physiology, Clinical Biochemistry, Pharmacology, folate, fibroblast, methotrexate, 03 medical and health sciences, 0302 clinical medicine, Dihydrofolate reductase, Medicine, Fibroblast, chemistry.chemical_classification, biology, business.industry, Cell Biology, medicine.disease, one-carbon metabolism, trisomy 21, 030104 developmental biology, Enzyme, medicine.anatomical_structure, chemistry, Cell culture, 030220 oncology & carcinogenesis, Toxicity, biology.protein, Methotrexate, business, Trisomy, medicine.drug
Abstract

Trisomy 21 causes Down syndrome (DS), the most common human genetic disorder and the leading genetic cause of intellectual disability. The alteration of one-carbon metabolism was described as the possible metabolic cause of the intellectual disability development in subjects with DS. One of the biochemical pathways involved in the one-carbon group transfer is the folate cycle. The cytotoxic drug methotrexate (MTX) is a folic acid (FA) analogue which inhibits the activity of dihydrofolate reductase enzyme involved in the one-carbon metabolic cycle. Trisomy 21 cells are more sensitive to the MTX effect than euploid cells, and in 1986 Jerome Lejeune and Coll. demonstrated that MTX was twice as toxic in trisomy 21 lymphocytes than in control cells. In the present work, the rescue effect on MTX toxicity mediated by FA and some of its derivatives, tetrahydrofolate (THF), 5-formyl-THF, and 5-methyl-THF, in both normal and trisomy 21 skin fibroblast cells, was evaluated. A statistically significant rescue effect was obtained by 5-formyl-THF, 5-methyl-THF, and their combination, administered together with MTX. In conclusion, trisomy 21 fibroblast cell lines showed a good response to the rescue effects of 5-formyl-THF and 5-methyl-THF on the MTX toxicity almost as normal cell lines.

Published
2018

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