7 results on '"Miano, Maria Giuseppina"'
Search Results
2. Novel missense mutations of TMPRSS3 in two consanguineous Tunisian families with non-syndromic autosomal recessive deafness
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Miano, Maria Giuseppina, Filippini, Francesco, Trujillo, Mariajos, Conte, Ivan, Lanzara, Carmela, Milln, Jos Maria, De Bernardo, Carmelilia, Grammatico, Barbara, Mangino, Massimo, Torrente, Isabella, Carrozzo, Romeo, Rinaldi, Ernesto, Ventruto, Valerio, Durso, Michele, Ayuso, Carmen, Ciccodicola, Alfredo, TESTA, Francesco, SIMONELLI, Francesca, Miano, Maria Giuseppina, Testa, Francesco, Filippini, Francesco, Trujillo, Mariajo, Conte, Ivan, Lanzara, Carmela, Milln, Jos Maria, De Bernardo, Carmelilia, Grammatico, Barbara, Mangino, Massimo, Torrente, Isabella, Carrozzo, Romeo, Simonelli, Francesca, Rinaldi, Ernesto, Ventruto, Valerio, Durso, Michele, Ayuso, Carmen, and Ciccodicola, Alfredo
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Comparative protein modeling ,Male ,Models, Molecular ,DFNB10 ,Chromosomes, Human, Pair 21 ,Genetic Linkage ,medicine.medical_treatment ,DNA Mutational Analysis ,Conserved sequence ,Protease, serine ,Consanguinity ,Genes, Recessive/genetics ,Serine Endopeptidases/chemistry/ genetics ,Missense mutation ,Membrane Protein ,Genetics (clinical) ,Conserved Sequence ,ddc:616 ,Genetics ,biology ,Linkage ,Mutation analysi ,Serine Endopeptidases ,Chromosomes, Human, Pair 21/genetics ,Chromosome Mapping ,Neoplasm Proteins ,Pedigree ,Serine protease ,Serine Endopeptidase ,Mutation (genetic algorithm) ,Female ,Conserved Sequence/genetics ,Human ,Tunisia ,Genotype ,Mutation, Missense/ genetics ,Hearing Loss, Sensorineural ,Molecular Sequence Data ,Hearing Loss, Sensorineural/congenital/ genetics ,Mutation, Missense ,Locus (genetics) ,Genes, Recessive ,DNA Mutational Analysi ,Neoplasm Protein ,Genetic ,Audiometry ,Genetic linkage ,DFNB8 ,Linkage (Genetics)/genetics ,medicine ,Humans ,Amino Acid Sequence ,Deafne ,Gene ,TMPRSS3 ,Protease ,Binding Sites ,Base Sequence ,Binding Site ,Membrane Proteins ,Molecular biology ,Protein Structure, Tertiary ,biology.protein ,Transmembrane protease, serine, 3 ,Non syndromic - Abstract
Recently the TMPRSS3 gene, which encodes a transmembrane serine protease, was found to be responsible for two non-syndromic recessive deafness loci located on human chromosome 21q22.3, DFNB8 and DFNB10. We found evidence for linkage to the DFNB8/10 locus in two unrelated consanguineous Tunisian families segregating congenital autosomal recessive sensorineural deafness. The audiometric tests showed a loss of hearing greater than 70 dB, in all affected individuals of both families. Mutation screening of TMPRSS3 revealed two novel missense mutations, W251C and P404L, altering highly conserved amino acids of the serine protease domain. Both mutations were not found in 200 control Tunisian chromosomes. The detection of naturally-occurring TMPRSS3 missense mutations in deafness families identifies functionally important amino acids. Comparative protein modeling of the TMPRSS3 protease domain predicted that W251C might lead to a structural rearrangement affecting the active site H257 and that P404L might alter the geometry of the active site loop and therefore affect the serine protease activity.
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- 2001
3. Microdeletion/duplication at the Xq28 IP locus causes a de novo IKBKG/NEMO/IKKgamma exon4_10 deletion in families with Incontinentia Pigmenti
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Paciolla Mariateresa, Lioi Maria Brigida, Zollino Marcella, Miano Maria Giuseppina, Gentile Mattia, Ayuso Carmen, Pescatore Alessandra, Fusco Francesca, D'Urso Michele, Ursini Matilde Valeria, and Faravelli Francesca
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Male ,Pseudogene ,Molecular Sequence Data ,IKBKG ,CNV ,Locus (genetics) ,IKKgamma ,Biology ,NEMO ,Gene Duplication ,Gene duplication ,Genetics ,medicine ,Humans ,Family ,Incontinentia Pigmenti ,Allele ,Somatic recombination ,Genetics (clinical) ,Sequence Deletion ,Chromosomes, Human, X ,Base Sequence ,Models, Genetic ,Exons ,Incontinentia pigmenti ,medicine.disease ,I-kappa B Kinase ,Pedigree ,Xq28 ,Female - Abstract
The Incontinentia Pigmenti (IP) locus contains the IKBKG/NEMO/IKKgamma gene and its truncated pseudogene copy, IKBKGP/deltaNEMO. The major genetic defect in IP is a heterozygous exon4_10 IKBKG deletion (IKBKGdel) caused by a recombination between two consecutive MER67B repeats. We analyzed 91 IP females carrying the IKBKGdel, 59 of whom carrying de novo mutations (65%). In eight parents, we found two recurrent nonpathological variants of IP locus, which were also present as rare polymorphism in control population: the IKBKGPdel, corresponding to the exon4_10 deletion in the pseudogene, and the MER67Bdup, that replicates the exon4_10 region downstream of the normal IKBKG gene. Using quantitative DNA analysis and microsatellite mapping, we established that both variants might promote the generation of the pathological IKBKGdel. Indeed, in family IP-516, the exon4_10 deletion was repositioned in the same allele from the pseudogene to the gene, whereas in family IP-688, the MER67Bdup generated the pathological IKBKGdel by recombination between two direct nonadjacent MER67Bs. Moreover, we found an instance of somatic recombination in a MER67Bdup variant, creating the IKBKGdel in an IP male. Our data suggest that the IP locus undergoes recombination producing recurrent variants that might be ''at risk'' of generating de novo IKBKGdel by NAHR during either meiotic or mitotic division.
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- 2009
4. Expanding the genetics and phenotypic spectrum of Lysine-specific demethylase 5C (KDM5C): a report of 13 novel variants
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Emanuela Leonardi, Maria Cristina Aspromonte, Denise Drongitis, Elisa Bettella, Lucia Verrillo, Roberta Polli, Meriel McEntagart, Laura Licchetta, Robertino Dilena, Stefano D’Arrigo, Claudia Ciaccio, Silvia Esposito, Vincenzo Leuzzi, Annalaura Torella, Demetrio Baldo, Fortunato Lonardo, Giulia Bonato, Serena Pellegrin, Franco Stanzial, Renata Posmyk, Ewa Kaczorowska, Miryam Carecchio, Monika Gos, Sylwia Rzońca-Niewczas, Maria Giuseppina Miano, Alessandra Murgia, Leonardi, Emanuela, Aspromonte, Maria Cristina, Drongitis, Denise, Bettella, Elisa, Verrillo, Lucia, Polli, Roberta, Mcentagart, Meriel, Licchetta, Laura, Dilena, Robertino, D'Arrigo, Stefano, Ciaccio, Claudia, Esposito, Silvia, Leuzzi, Vincenzo, Torella, Annalaura, Baldo, Demetrio, Lonardo, Fortunato, Bonato, Giulia, Pellegrin, Serena, Stanzial, Franco, Posmyk, Renata, Kaczorowska, Ewa, Carecchio, Miryam, Gos, Monika, Rzońca-Niewczas, Sylwia, Miano, Maria Giuseppina, and Murgia, Alessandra
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Genetics ,Genetics (clinical) - Abstract
Lysine-specific demethylase 5C (KDM5C) has been identified as an important chromatin remodeling gene, contributing to X-linked neurodevelopmental disorders (NDDs). The KDM5C gene, located in the Xp22 chromosomal region, encodes the H3K4me3-me2 eraser involved in neuronal plasticity and dendritic growth. Here we report 30 individuals carrying 13 novel and one previously identified KDM5C variants. Our cohort includes the first reported case of somatic mosaicism in a male carrying a KDM5C nucleotide substitution, and a dual molecular finding in a female carrying a homozygous truncating FUCA1 alteration together with a de novo KDM5C variant. With the use of next generation sequencing strategies, we detected 1 frameshift, 1 stop codon, 2 splice-site and 10 missense variants, which pathogenic role was carefully investigated by a thorough bioinformatic analysis. The pattern of X-chromosome inactivation was found to have an impact on KDM5C phenotypic expression in females of our cohort. The affected individuals of our case series manifested a neurodevelopmental condition characterized by psychomotor delay, intellectual disability with speech disorders, and behavioral features with particular disturbed sleep pattern; other observed clinical manifestations were short stature, obesity and hypertrichosis. Collectively, these findings expand the current knowledge about the pathogenic mechanisms leading to dysfunction of this important chromatin remodeling gene and contribute to a refinement of the KDM5C phenotypic spectrum.
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- 2022
5. Histone demethylase KDM5C is a SAHA-sensitive central hub at the crossroads of transcriptional axes involved in multiple neurodevelopmental disorders
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Stefania Filosa, Jesper Christensen, Cheryl Shoubridge, Maria Giuseppina Miano, Agnese Padula, Lucia Altucci, Kristian Helin, Elia Di Schiavi, Lucia Verrillo, Loredana Poeta, Benedetta Attianese, Jozef Gecz, Mariaelena Valentino, Hans van Bokhoven, Maria Brigida Lioi, Patrick Collombat, Charles E. Schwartz, Adriano Barra, Poeta, Loredana, Padula, Agnese, Attianese, Benedetta, Valentino, Mariaelena, Verrillo, Lucia, Filosa, Stefania, Shoubridge, Cheryl, Barra, Adriano, Schwartz, Charles E, Christensen, Jesper, van Bokhoven, Han, Helin, Kristian, Lioi, Maria Brigida, Collombat, Patrick, Gecz, Jozef, Altucci, Lucia, Di Schiavi, Elia, and Miano, Maria Giuseppina
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Male ,0301 basic medicine ,medicine.drug_class ,Methylation ,Cell Line ,Histones ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,Animals ,Humans ,Epigenetics ,Caenorhabditis elegans ,Promoter Regions, Genetic ,Molecular Biology ,Transcription factor ,Genetics (clinical) ,Histone Demethylases ,Homeodomain Proteins ,Mice, Knockout ,Neurons ,epigenetics, KDM, human diseases ,Vorinostat ,biology ,Effector ,Histone deacetylase inhibitor ,General Medicine ,Cell biology ,Chromatin ,DNA-Binding Proteins ,Histone Deacetylase Inhibitors ,Mice, Inbred C57BL ,HEK293 Cells ,030104 developmental biology ,Histone ,Neurodevelopmental Disorders ,Mutation ,KDM5C ,biology.protein ,H3K4me3 ,Demethylase ,Female ,General Article ,030217 neurology & neurosurgery ,Signal Transduction ,Transcription Factors - Abstract
A disproportional large number of neurodevelopmental disorders (NDDs) is caused by variants in genes encoding transcription factors and chromatin modifiers. However, the functional interactions between the corresponding proteins are only partly known. Here, we show that KDM5C, encoding a H3K4 demethylase, is at the intersection of transcriptional axes under the control of three regulatory proteins ARX, ZNF711 and PHF8. Interestingly, mutations in all four genes (KDM5C, ARX, ZNF711 and PHF8) are associated with X-linked NDDs comprising intellectual disability as a core feature. in vitro analysis of the KDM5C promoter revealed that ARX and ZNF711 function as antagonist transcription factors that activate KDM5C expression and compete for the recruitment of PHF8. Functional analysis of mutations in these genes showed a correlation between phenotype severity and the reduction in KDM5C transcriptional activity. The KDM5C decrease was associated with a lack of repression of downstream target genes Scn2a, Syn1 and Bdnf in the embryonic brain of Arx-null mice. Aiming to correct the faulty expression of KDM5C, we studied the effect of the FDA-approved histone deacetylase inhibitor suberanilohydroxamic acid (SAHA). In Arx-KO murine ES-derived neurons, SAHA was able to rescue KDM5C depletion, recover H3K4me3 signalling and improve neuronal differentiation. Indeed, in ARX/alr-1-deficient Caenorhabditis elegans animals, SAHA was shown to counteract the defective KDM5C/rbr-2-H3K4me3 signalling, recover abnormal behavioural phenotype and ameliorate neuronal maturation. Overall, our studies indicate that KDM5C is a conserved and druggable effector molecule across a number of NDDs for whom the use of SAHA may be considered a potential therapeutic strategy.
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- 2019
6. Heterozygosity mapping by quantitative fluorescent PCR reveals an interstitial deletion in Xq26.2-q28 associated with ovarian dysfunction
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Maria Giuseppina Miano, Michele D'Urso, Giorgia Fimiani, Matilde Valeria Ursini, Valerio Ventruto, Geppino Falco, Carmela Laperuta, Fimiani, Giorgia, Laperuta, Carmela, Falco, Geppino, Ventruto, Valerio, D'Urso, Michele, Ursini, Matilde Valeria, and Miano, Maria Giuseppina
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Adult ,medicine.medical_specialty ,Premature ovarian failure syndrome ,endocrine system diseases ,Heterozygosity mapping ,Genotype ,Menopause, Premature ,Biology ,Primary Ovarian Insufficiency ,Polymerase Chain Reaction ,X-inactivation ,Loss of heterozygosity ,Xq26.2-Xq28 ,X Chromosome Inactivation ,medicine ,Humans ,Skewed X-inactivation ,X chromosome ,Genetics ,Chromosomes, Human, X ,Genetic Carrier Screening ,Rehabilitation ,Cytogenetics ,Obstetrics and Gynecology ,Chromosome Mapping ,Quantitative fluorescent PCR ,medicine.disease ,Penetrance ,female genital diseases and pregnancy complications ,Xq28 ,Premature ovarian failure ,Pedigree ,XCI ,Reproductive Medicine ,Karyotyping ,Female ,Chromosome Deletion ,Microsatellite Repeats - Abstract
Background: Deletions of Xq chromosome are reported for a number of familial conditions exhibiting premature ovarian failure (POF) and early menopause (EM). Methods and results: We describe the inheritance of an interstitial deletion of the long arm of the X chromosome associated with either POF or EM in the same family. Cytogenetic studies and heterozygosity mapping by quantitative fluorescent PCR revealed a 46,X,del(X)(q26.2-q28) karyotype in a POF female, in her EM mother, and also in her aborted fetus with severe cardiopathy. Applying a microsatellite approach, we have narrowed the extension of an identical interstitial deletion located between DXS1187 and DXS1073. These data, in line with other mapped deletions, single out the proximal Xq28 as the region most frequently involved in ovarian failure. We also propose that other factors may influence the phenotypic effect of this alteration. Indeed, skewed X inactivation has been ascertained in EM and POF to be associated with different X haplotypes. Conclusion: Our analysis indicates that Xq26.2-q28 deletion is responsible for gonad dysgenesis in a family with EM/POF. The dissimilar deletion penetrance may be due to epigenetic modifications of other X genes that can contribute to human reproduction, highlighting that ovarian failure should be considered as a multifactorial disease. © The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
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- 2005
7. Mapping of MRX81 in Xp11.2-Xq12 suggests the presence of a new gene involved in nonspecific X-linked mental retardation
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Maria Michela Rinaldi, Carmela Lanzara, Valerio Ventruto, Michele D'Urso, Ida Annunziata, Alberto Zullo, Ivan Conte, Giorgio Casari, Alfredo Ciccodicola, Maria Giuseppina Miano, Annunziata, I, Lanzara, C, Conte, I, Zullo, A, Ventruto, V, Rinaldi, Mm, D'Urso, M, Casari, GIORGIO NEVIO, Ciecodicola, A, Miano, Mg, Annunziata, Ida, Lanzara, Carmela, Conte, Ivan, Zullo, Alberto, Ventruto, Valerio, Rinaldi, Maria Michela, D'Urso, Michele, Casari, Giorgio, Ciccodicola, Alfredo, and Miano, Maria Giuseppina
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Male ,Genotype ,Genetic Linkage ,DNA Mutational Analysis ,Exon ,linkage genetico ,Locus (genetics) ,Ephrin-B1 ,Biology ,DNA Mutational Analysi ,Genetic linkage ,Haplotype ,Cytoskeletal Protein ,Humans ,Allele ,Malattia X-linked ,Gene ,Alleles ,Genetics (clinical) ,X chromosome ,Nuclear Protein ,Centrosome ,Family Health ,Recombination, Genetic ,Genetics ,Chromosomes, Human, X ,Models, Genetic ,GTPase-Activating Protein ,GTPase-Activating Proteins ,Nuclear Proteins ,Chromosome Mapping ,Exons ,Phosphoproteins ,Pedigree ,Cytoskeletal Proteins ,Ritardo mentale ,Haplotypes ,Databases as Topic ,Genetic marker ,Phosphoprotein ,Mental Retardation, X-Linked ,Female ,Lod Score ,5-Aminolevulinate Synthetase ,Human - Abstract
X-linked nonspecific mental retardation (MRX) accounts for similar to25% of mental retardation in males. A number of MRX loci have been mapped on the X chromosome, reflecting the complexity of gene action in central nervous system (CNS) specification and function. Eleven MRX genes have been identified, but many other causative loci remain to be refined to the single gene level. In 21 MRX families, the causative gene is located in the pericentromeric region; and we report here the identification by linkage analysis of a further such locus, MRX81. The new MRX locus was identified by two- and multi-point parametric analysis carried out on a large Italian family. Tight linkage of MRX81 to DNA markers ALAS2, DXS991, and DXS7132 was observed with a maximum LOD score of 3.43. Haplotype construction delineates an MRX81 critical region of 8 cM, the smallest MRX pericentromeric interval so far described, between DXS1039 and DXS1216, and placing it in Xp11.2-Xq12. So far, automated sequencing of two candidates in the region, the MRX gene oligophrenin (OPHN1) and the brain-specific ephrinB1 (EFNB1) gene, in DNA from affected males excluded their candidacy for MRX81, suggesting a novel disease gene. (C) 2003 Wiley-Liss, Inc.
- Published
- 2003
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