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334 results on '"Chessa, Luciana"'

1. Progressive Depletion of B and T Lymphocytes in Patients with Ataxia Telangiectasia: Results of the Italian Primary Immunodeficiency Network

Author

Cirillo, Emilia, Polizzi, Agata, Soresina, Annarosa, Prencipe, Rosaria, Giardino, Giuliana, Cancrini, Caterina, Finocchi, Andrea, Rivalta, Beatrice, Dellepiane, Rosa M., Baselli, Lucia A., Montin, Davide, Trizzino, Antonino, Consolini, Rita, Azzari, Chiara, Ricci, Silvia, Lodi, Lorenzo, Quinti, Isabella, Milito, Cinzia, Leonardi, Lucia, Duse, Marzia, Carrabba, Maria, Fabio, Giovanna, Bertolini, Patrizia, Coccia, Paola, D’Alba, Irene, Pession, Andrea, Conti, Francesca, Zecca, Marco, Lunardi, Claudio, Bianco, Manuela Lo, Presti, Santiago, Sciuto, Laura, Micheli, Roberto, Bruzzese, Dario, Lougaris, Vassilios, Badolato, Raffaele, Plebani, Alessandro, Chessa, Luciana, and Pignata, Claudio

Published
2022
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3. The Italian Registry for Primary Immunodeficiencies (Italian Primary Immunodeficiency Network; IPINet): Twenty Years of Experience (1999–2019)

Author

Lougaris, Vassilios, Pession, Andrea, Baronio, Manuela, Soresina, Annarosa, Rondelli, Roberto, Gazzurelli, Luisa, Benvenuto, Alessio, Martino, Silvana, Gattorno, Marco, Biondi, Andrea, Zecca, Marco, Marinoni, Maddalena, Fabio, Giovanna, Aiuti, Alessandro, Marseglia, Gianluigi, Putti, Maria Caterina, Agostini, Carlo, Lunardi, Claudio, Tommasini, Alberto, Bertolini, Patrizia, Gambineri, Eleonora, Consolini, Rita, Matucci, Andrea, Azzari, Chiara, Danieli, Maria Giovanna, Paganelli, Roberto, Duse, Marzia, Cancrini, Caterina, Moschese, Viviana, Chessa, Luciana, Spadaro, Giuseppe, Civino, Adele, Vacca, Angelo, Cardinale, Fabio, Martire, Baldassare, Carpino, Luigi, Trizzino, Antonino, Russo, Giovanna, Cossu, Fausto, Badolato, Raffaele, Pietrogrande, Maria Cristina, Quinti, Isabella, Rossi, Paolo, Ugazio, Alberto, Pignata, Claudio, and Plebani, Alessandro

Published
2020
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8. Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism

Author

Reynolds, John J, Bicknell, Louise S, Carroll, Paula, Higgs, Martin R, Shaheen, Ranad, Murray, Jennie E, Papadopoulos, Dimitrios K, Leitch, Andrea, Murina, Olga, Tarnauskaitė, Žygimantė, Wessel, Sarah R, Zlatanou, Anastasia, Vernet, Audrey, von Kriegsheim, Alex, Mottram, Rachel M A, Logan, Clare V, Bye, Hannah, Li, Yun, Brean, Alexander, Maddirevula, Sateesh, Challis, Rachel C, Skouloudaki, Kassiani, Almoisheer, Agaadir, Alsaif, Hessa S, Amar, Ariella, Prescott, Natalie J, Bober, Michael B, Duker, Angela, Faqeih, Eissa, Seidahmed, Mohammed Zain, Al Tala, Saeed, Alswaid, Abdulrahman, Ahmed, Saleem, Al-Aama, Jumana Yousuf, Altmüller, Janine, Al Balwi, Mohammed, Brady, Angela F, Chessa, Luciana, Cox, Helen, Fischetto, Rita, Heller, Raoul, Henderson, Bertram D, Hobson, Emma, Nürnberg, Peter, Percin, E Ferda, Peron, Angela, Spaccini, Luigina, Quigley, Alan J, Thakur, Seema, Wise, Carol A, Yoon, Grace, Alnemer, Maha, Tomancak, Pavel, Yigit, Gökhan, Taylor, A Malcolm R, Reijns, Martin A M, Simpson, Michael A, Cortez, David, Alkuraya, Fowzan S, Mathew, Christopher G, Jackson, Andrew P, and Stewart, Grant S

Published
2017
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11. Ataxia-Telangiectasia

Author

Chessa, Luciana, Polizzi, Agata, Ruggieri, Martino, Ruggieri, Martino, editor, Pascual-Castroviejo, Ignacio, editor, and Di Rocco, Concezio, editor

Published
2008
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14. P53 centrosomal localization diagnoses ataxia-telangiectasia homozygotes and heterozygotes

Author

Prodosmo, Andrea, De Amicis, Andrea, Nistico, Cecilia, Gabriele, Mario, Di Rocco, Giuliana, Monteonofrio, Laura, Piane, Maria, Cundari, Enrico, Chessa, Luciana, and Soddu, Silvia

Subjects
Gene mutations -- Physiological aspects -- Research, Ataxia telangiectasia -- Genetic aspects -- Diagnosis -- Care and treatment -- Research, Genetic screening -- Usage, Health care industry
Abstract

Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder characterized by radiosensitivity, genomic instability, and predisposition to cancer. A-T is caused by biallelic mutations in the ataxia-telangiectasia mutated (ATM) gene, but [...]

Published
2013
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17. Clinical delineation of fetal alcohol spectrum disorders (FASD) in Italian children: Comparison and contrast with other racial/ethnic groups and implications for diagnosis and prevention

Author

Ceccanti, Mauro, Alessandra Spagnolo, Primavera, Tarani, Luigi, Luisa Attilia, Maria, Chessa, Luciana, Mancinelli, Rosanna, Stegagno, Michele, Francesco Sasso, Guido, Romeo, Marina, Jones, Kenneth L., Robinson, Luther K., del Campo, Miguel, Phillip Gossage, J., May, Philip A., and Eugene Hoyme, H.

Published
2007
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20. Consensus of the Italian Primary Immunodeficiency Network on transition management from pediatric to adult care in patients affected with childhood-onset inborn errors of immunity

Author

Cirillo, Emilia, primary, Giardino, Giuliana, additional, Ricci, Silvia, additional, Moschese, Viviana, additional, Lougaris, Vassilios, additional, Conti, Francesca, additional, Azzari, Chiara, additional, Barzaghi, Federica, additional, Canessa, Clementina, additional, Martire, Baldassarre, additional, Badolato, Raffaele, additional, Dotta, Laura, additional, Soresina, Annarosa, additional, Cancrini, Caterina, additional, Finocchi, Andrea, additional, Montin, Davide, additional, Romano, Roberta, additional, Amodio, Donato, additional, Ferrua, Francesca, additional, Tommasini, Alberto, additional, Baselli, Lucia Augusta, additional, Dellepiane, Rosa Maria, additional, Polizzi, Agata, additional, Chessa, Luciana, additional, Marzollo, Antonio, additional, Cicalese, Maria Pia, additional, Putti, Maria Caterina, additional, Pession, Andrea, additional, Aiuti, Alessandro, additional, Locatelli, Franco, additional, Plebani, Alessandro, additional, and Pignata, Claudio, additional

Published
2020
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24. Splicing defects in the ataxia-telangiectasia gene, ATM: underlying mutations and consequences

Author

Teraoka, Sharon N., Telatar, Milhan, Becker-Catania, Sara, Liang, Teresa, Onengut, Suna, Tolun, Asli, Chessa, Luciana, Sanal, Ozden, Bernatowska, Eva, Gatti, Richard A., and Concannon, Patrick

Subjects
Ataxia telangiectasia -- Genetic aspects, Biological sciences
Abstract

The frequency of splicing mutations was studied in an independent population of people with ataxia telangiectasia (AT). Sixty-two mutations were found, of which 30 (48%) affected splicing accuracy. Ten of the 30 mutations involved canonical splice sites. Novel splice sites were created by three of the mutations. In addition, nonsense and missense mutations were identified that indirectly affected splicing. There were also cases of variant splicing in which no underlying mutation was found.

Published
1999

26. Genotype-phenotype relationships in ataxia-telangiectasia and variants

Author

Gilad, Shlomit, Chessa, Luciana, Khosravi, Rami, Russell, Pamela, Galanty, Yaron, Piane, Maria, Gatti, Richard A., Jorgensen, Timothy J., Shiloh, Yosef, and Bar-Shira, Anat

Subjects
Genetic disorders -- Research, Chromosome mapping -- Usage, Ataxia telangiectasia -- Genetic aspects, Cellular signal transduction -- Research, Biological sciences
Abstract

Ataxia-telangiectasia (A-T) has ATM as the underlying gene. It encodes a large protein kinase with a phosphatidylinositol 3-kinase-like domain. ATM protein levels have been measured in six A-T variants and the ATM genes searched for mutations. Findings show there is a larger range of phenotypes associated with ATM mutations than had been known and show that some A-T variant phenotypes come from ATM mutations. Some of those are without telangiectasia. A-T is a complex multisystem autosomal recessive disorder.

Published
1998

27. Ataxia-telangiectasia: identification and detection of founder-effect mutations in the ATM gene in ethnic populations

Author

Telatar, Milhan, Teraoka, Sharon, Wang, Zhijun, Chun, Helen H., Liang, Teresa, Castellvi-Bel, Sergi, Udar, Nitin, Borressen-Dale, Anne-Lise, Chessa, Luciana, Bernatowska-Matuszkiewicz, Eva, Porras, Oscar, Watanabe, Mitsunori, Junker, Anne, Concannon, Patrick, and Gatti, Richard A.

Subjects
Ataxia telangiectasia -- Genetic aspects, Human population genetics -- Research, Biological sciences
Abstract

Ten ethnic populations have been studied to determine common mutations in the ATM gene associated with ataxia-telangiectasia (A-T). Ninety-two truncating mutations were found by screening 140 mutant alleles. Founder-effect mutations were found in Costa Rican, Norwegian, Polish, Italian and Amish/Mennonite populations. Genomic mutations and effects on cDNA were examined to enable assessment of ATM heterozygotes in relation to susceptibility to other diseases.

Published
1998

28. SMC1 involvement in fragile site expression

Author

Musio, Antonio, Montagna, Cristina, Mariani, Tullio, Tilenni, Manuela, Focarelli, Maria Luisa, Brait, Lorenzo, Indino, Esterina, Benedetti, Pier Alberto, Chessa, Luciana, Albertini, Alberto, Ried, Thomas, and Vezzoni, Paolo

Published
2005

31. Genotype-phenotype correlations in ataxia telangiectasia patients with ATM c.3576G > A and c.8147T > C mutations

Author

Os, N.J.H. van, Chessa, Luciana, Weemaes, C.M.R., Deuren, M. van, Fievet, Alice, Gaalen, J. van, Roeleveld, N., Warrenburg, B.P.C. van de, Doerk, Thilo, Willemsen, M.A.A.P., Os, N.J.H. van, Chessa, Luciana, Weemaes, C.M.R., Deuren, M. van, Fievet, Alice, Gaalen, J. van, Roeleveld, N., Warrenburg, B.P.C. van de, Doerk, Thilo, and Willemsen, M.A.A.P.

Abstract

Contains fulltext : 203873.pdf (publisher's version ) (Closed access)

Published
2019

34. A single ataxia telangiectasia gene with a product similar to Pl-3 kinase

Author

Savitsky, Kinneret, Bar-Shira, Anat, Gilad, Shlomit, Rotman, Galit, Ziv, Yael, Vanagaite, Lina, Tagle, Danilo A., Smith, Sara, Uziel, Tamar, Sfez, Sharon, Ashkenazi, Maya, Pecker, Iris, Frydman, Moshe, Harnik, Reli, Patanjali, Sankhavaram R., Simmons, Andrew, Clines, Gregory A., Sartiel, Adam, Gatti, Richard A., Chessa, Luciana, Sanal, Ozden, Lavin, Martin F., Jaspers, N.G.J., Taylor, A. Malcolm R., Arlett, Colin F., Miki, Toru, Weissman, Sherman M., Lovett, Michael, Collins, Francis, and Shiloh, Yosef

Subjects
Ataxia telangiectasia -- Genetic aspects, Cancer -- Genetic aspects, Science and technology, Genetic aspects
Abstract

A gene, ATM, that is mutated in the autosomal recessive disorder ataxia telangiectasia (AT) was identified by positional cloning on chromosome 11q22-23. AT is characterized by cerebellar degeneration, immunodeficiency, chromosomal instability, cancer predisposition, radiation sensitivity, and cell cycle abnormalities. The disease is genetically heterogeneous, with four complementation groups that have been suspected to represent different genes. ATM, which has a transcript of 12 kilobases, was found to be mutated in AT patients from all complementation groups, indicating that it is probably the sole gene responsible for this disorder. A partial ATM complementary DNA clone of 5.9 kilobases encoded a putative protein that is similar to several yeast and mammalian phosphati-dylinositol-3' kinases that are involved in mitogenic signal transduction, meiotic recombination, and cell cycle control. The discovery of ATM should enhance understanding of AT and related syndromes and may allow the identification of AT heterozygotes, who are at increased risk of cancer., Ataxia telangiectasia is inherited in a monogenic, autosomal recessive manner, with a worldwide incidence of 1 in 40,000 to 1 in 100,000 [1]. Ataxia telangiectasia is usually first noticed in [...]

Published
1995

37. Ataxia-telangiectasia

Author

Leuzzi, Vincenzo, D'Agnano, Daniela, Menotta, Michele, Caputi, Caterina, Chessa, Luciana, and Magnani, Mauro

Subjects
Article
Abstract

Objective Ataxia-telangiectasia (AT) is a rare, severe, and ineluctably progressive multisystemic neurodegenerative disease. Variant AT phenotypes have been described in patients with mild- and late-onset neurologic deterioration and atypical features (dystonia and myoclonus). We report on the clinical characteristics and transcriptome profile of patients with a typical AT presentation and genotype who experienced an unexpected favorable course. Methods A 24-year-old woman developed, by the age of 3 years, all the classic symptoms of AT associated with increased alpha-fetoprotein levels, a compound AT-mutated (ATM) genotype with an inframe deletion c.2250G>A (p.Glu709_Lys750del42) and a missense mutation c.8122G>A (p.Asp2708Gln), and no residual ATM protein expression. By the age of 12 years, ataxia slowly disappeared, and a very mild choreic disorder was the only neurologic feature in adulthood. Brain MRI was normal. The blood transcriptome profile was assessed and compared with that of healthy controls and patients with the classic AT phenotype. Results The atypical clinical course of the patient was associated with a transitional transcriptome profile: while 90% of transcripts were expressed as in patients with the classic AT presentation, 10% of transcripts were expressed as in healthy controls. Conclusions The unexpected mild clinical outcome and transcriptome profile of this patient with AT suggest the existence of individual resilience to the altered ATM synthesis. Because of their possible prognostic and therapeutic implications, the identification of modifier factors affecting the phenotype would deserve further studies.

Published
2018

40. Genotype–phenotype correlations in ataxia telangiectasia patients with ATM c.3576G>A and c.8147T>C mutations

Author

van Os, Nienke J H, primary, Chessa, Luciana, additional, Weemaes, Corry M R, additional, van Deuren, Marcel, additional, Fiévet, Alice, additional, van Gaalen, Judith, additional, Mahlaoui, Nizar, additional, Roeleveld, Nel, additional, Schrader, Christoph, additional, Schindler, Detlev, additional, Taylor, Alexander M R, additional, Van de Warrenburg, Bart P C, additional, Dörk, Thilo, additional, and Willemsen, Michèl A A P, additional

Published
2019
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42. Cutaneous granulomatosis and combined immunodeficiency revealing Ataxia-Telangiectasia: a case report

Author

Antoccia Antonio, Ferrari Francesca, Angelino Giulia, Scarselli Alessia, Folgori Laura, Chessa Luciana, and Finocchi Andrea

Subjects
Pediatrics, RJ1-570
Abstract

Abstract Ataxia-telangiectasia (A-T) is a complex multisystem disorder characterized by progressive neurological impairment, variable immunodeficiency and oculo-cutaneous telangiectasia. A-T is a member of chromosomal breakage syndromes and it is caused by a mutation in the ataxia-telangiectasia mutated (ATM) gene. Because of a wide clinical heterogeneity, A-T is often difficult to diagnose in children. We report an unusual case of a 3-year-old boy affected by A-T who presented exclusively with extensive cutaneous granulomatosis and severe combined immunodeficiency, without neurological abnormalities, at the time of diagnosis. This case clearly emphasizes the variable presentation of A-T syndrome and highlights the difficulties in the early diagnosis of A-T. A-T should be considered in children with evidence of combined humoral and cellular immunodeficiency associated with unexplained skin granulomatous lesions, even in the absence of the classic features of this syndrome.

Published
2010
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44. Gelastic epilepsy: a clinical contribution

Author

Iannetti, Paola, Chessa, Luciana, Raucci, Umberto, Basile, Luciano A., Fantozzi, Luigi M., and Bozzao, Luigi

Subjects
Epilepsy in children -- Physiological aspects, Hypothalamus -- Physiological aspects, Hamartoma -- Diagnosis, Pituitary gland tumors -- Physiological aspects, Health
Published
1992

45. Clinical and genetic studies in a family with a new splice-site mutation in the choroideremia gene

Author

Contestabile, Maria Teresa, Piane, Maria, Cascone Nc, Pasquale N., Cascone, N. C., Pasquale, N., Ciarnella, Angela, Recupero, Santi Maria, and Chessa, Luciana

Subjects
Adult, Male, Adolescent, Fundus Oculi, DNA Mutational Analysis, Immunoblotting, Middle Aged, Pedigree, Young Adult, Phenotype, Italy, Mutation, Electroretinography, Humans, Family, Female, RNA Splice Sites, Fluorescein Angiography, Visual Fields, Child, Choroideremia, Tomography, Optical Coherence, Research Article, Adaptor Proteins, Signal Transducing, Aged
Abstract

Purpose To describe the clinical and molecular findings of an Italian family with a new mutation in the choroideremia (CHM) gene. Methods We performed a comprehensive ophthalmologic examination, fundus photography, macular optical coherence tomography, perimetry, electroretinography, and fluorescein angiography in an Italian family. The clinical diagnosis was supported by western blot analysis of lymphoblastoid cell lines from patients with CHM and carriers, using a monoclonal antibody against the 415 C-terminal amino acids of Rab escort protein-1 (REP-1). Sequencing of the CHM gene was undertaken on genomic DNA from affected men and carriers; the RNA transcript was analyzed with reverse transcriptase-PCR. Results The affected men showed a variability in the rate of visual change and in the degree of clinical and functional ophthalmologic involvement, mainly age-related, while the women displayed aspecific areas of chorioretinal degeneration. Western blot did not show a detectable amount of normal REP-1 protein in affected men who were hemizygous for a novel mutation, c.819+2T>A at the donor splicing site of intron 6 of the CHM gene; the mutation was confirmed in heterozygosity in the carriers. Conclusions Western blot of the REP-1 protein confirmed the clinical diagnosis, and molecular analysis showed the new in-frame mutation, c.819+2T>A, leading to loss of function of the REP-1 protein. These results emphasize the value of a diagnostic approach that correlates genetic and ophthalmologic data for identifying carriers in families with CHM. An early diagnosis might be crucial for genetic counseling of this type of progressive and still untreatable disease.

Published
2014

47. Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism

Author

Reynolds, John J., Bicknell, Louise S., Carroll, Paula, Higgs, Martin R., Shaheen, Ranad, Murray, Jennie E., Papadopoulos, Dimitrios K., Leitch, Andrea, Murina, Olga, Tarnauskaite, Zygimante, Wessel, Sarah R., Zlatanou, Anastasia, Vernet, Audrey, von Kriegsheim, Alex, Mottram, Rachel M. A., Logan, Clare V., Bye, Hannah, Li, Yun, Brean, Alexander, Maddirevula, Sateesh, Challis, Rachel C., Skouloudaki, Kassiani, Almoisheer, Agaadir, Alsaif, Hessa S., Amar, Ariella, Prescott, Natalie J., Bober, Michael B., Duker, Angela, Faqeih, Eissa, Seidahmed, Mohammed Zain, Al Tala, Saeed, Alswaid, Abdulrahman, Ahmed, Saleem, Al-Aama, Jumana Yousuf, Altmueller, Janine, Al Balwi, Mohammed, Brady, Angela F., Chessa, Luciana, Cox, Helen, Fischetto, Rita, Heller, Raoul, Henderson, Bertram D., Hobson, Emma, Nurnberg, Peter, Percin, E. Ferda, Peron, Angela, Spaccini, Luigina, Quigley, Alan J., Thakur, Seema, Wise, Carol A., Yoon, Grace, Alnemer, Maha, Tomancak, Pavel, Yigit, Goekhan, Taylor, A. Malcolm R., Reijns, Martin A. M., Simpson, Michael A., Cortez, David, Alkuraya, Fowzan S., Mathew, Christopher G., Jackson, Andrew P., Stewart, Grant S., Reynolds, John J., Bicknell, Louise S., Carroll, Paula, Higgs, Martin R., Shaheen, Ranad, Murray, Jennie E., Papadopoulos, Dimitrios K., Leitch, Andrea, Murina, Olga, Tarnauskaite, Zygimante, Wessel, Sarah R., Zlatanou, Anastasia, Vernet, Audrey, von Kriegsheim, Alex, Mottram, Rachel M. A., Logan, Clare V., Bye, Hannah, Li, Yun, Brean, Alexander, Maddirevula, Sateesh, Challis, Rachel C., Skouloudaki, Kassiani, Almoisheer, Agaadir, Alsaif, Hessa S., Amar, Ariella, Prescott, Natalie J., Bober, Michael B., Duker, Angela, Faqeih, Eissa, Seidahmed, Mohammed Zain, Al Tala, Saeed, Alswaid, Abdulrahman, Ahmed, Saleem, Al-Aama, Jumana Yousuf, Altmueller, Janine, Al Balwi, Mohammed, Brady, Angela F., Chessa, Luciana, Cox, Helen, Fischetto, Rita, Heller, Raoul, Henderson, Bertram D., Hobson, Emma, Nurnberg, Peter, Percin, E. Ferda, Peron, Angela, Spaccini, Luigina, Quigley, Alan J., Thakur, Seema, Wise, Carol A., Yoon, Grace, Alnemer, Maha, Tomancak, Pavel, Yigit, Goekhan, Taylor, A. Malcolm R., Reijns, Martin A. M., Simpson, Michael A., Cortez, David, Alkuraya, Fowzan S., Mathew, Christopher G., Jackson, Andrew P., and Stewart, Grant S.

Abstract

To ensure efficient genome duplication, cells have evolved numerous factors that promote unperturbed DNA replication and protect, repair and restart damaged forks. Here we identify downstream neighbor of SON (DONSON) as a novel fork protection factor and report biallelic DONSON mutations in 29 individuals with microcephalic dwarfism. We demonstrate that DONSON is a replisome component that stabilizes forks during genome replication. Loss of DONSON leads to severe replication-associated DNA damage arising from nucleolytic cleavage of stalled replication forks. Furthermore, ATM- and Rad3-related (ATR)-dependent signaling in response to replication stress is impaired in DONSON-deficient cells, resulting in decreased checkpoint activity and the potentiation of chromosomal instability. Hypomorphic mutations in DONSON substantially reduce DONSON protein levels and impair fork stability in cells from patients, consistent with defective DNA replication underlying the disease phenotype. In summary, we have identified mutations in DONSON as a common cause of microcephalic dwarfism and established DONSON as a critical replication fork protein required for mammalian DNA replication and genome stability.

Published
2017

49. Relevance of reactive oxygen and nitrogen species interaction in Leber’s hereditary optic neuropathy

Author

Falabella, Micol, Forte, Elena, Magnifico, Maria Chiara, Santini, Paolo, Arese, Marzia, Giuffrè, Alessandro, Radić, Kristina, Chessa, Luciana, Coarelli, Giulia, Buscarinu, Maria Chiara, Mechelli, Rosella, Salvetti, Marco, and Sarti, Paolo

Subjects
Leber’s hereditary optic neuropathy, nitric oxide, genetic structures, eye diseases
Abstract

Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disorder caused by point mutations in complex I subunit genes and characterized by the preferential loss of retinal ganglion cells, leading to optic nerve degeneration [1, 2]. The mechanisms of LHON pathogenesis are still not well understood ; cell and animal models point to oxidative stress and impairment of redox homeostasis as important factors contributing to LHON pathophysiology. Long-term exposure to nitric oxide (NO) is known to impair mitochondrial proteins, leading to persistent inhibition of mitochondrial function and to cell death. We have collected evidence that allowed us to hypothesize that chronic changes in the NO homeostasis could contribute to cell dysfunction in LHON patients [3]. We found that peripheral blood mononuclear cells, derived from a female LHON patient with bilateral reduced vision and carrying the pathogenic mutation 11778/ND4, display increased cellular levels of reactive oxygen and nitrogen species, with accumulation of nitrite/nitrate and 3- nitrotyrosine. Moreover, we show that lymphoblasts from the same patient are more susceptible to prolonged NO exposure. These unprecedented observations suggest that oxidative and nitrosative stress can play a role in driving the pathology when excess NO is available.

Published
2016

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