31 results on '"Sorrentino U"'
Search Results
2. Inhibition of nitric oxide synthase expression by methanolic extract of Crescentia alata and its derived flavonols
- Author
-
Marzocco, Stefania, Autore, Giuseppina, Rastrelli, Luca, Lauro, Maria Rosaria, Sorrentino, R., Sorrentino, U., Aquino, Rita Patrizia, and Pinto, Aldo
- Published
- 2001
3. Regulation of inducile nitric oxide synthase expression by methylguanidine, an uremic catabolyte
- Author
-
Autore, Giuseppina, Marzocco, Stefania, Sorrentino, R., Sorrentino, U., Turco, M. C., and Pinto, Aldo
- Published
- 2001
4. Gastric B-Cell Clonal Expansion andHelicobacter pyloriInfection in Patients with Autoimmune Diseases and with Dyspepsia: A Follow-up Study
- Author
-
Sorrentino, U., primary, Ferraccioll, G. F., additional, Devita, S., additional, Labombarda, A., additional, Avellini, C., additional, Ponzetto, A., additional, Beltrami, C. A., additional, Boiocchi, M., additional, and Bartoli, E., additional
- Published
- 1997
- Full Text
- View/download PDF
5. Gastric B-Cell Clonal Expansion and Helicobacter pylori Infection in Patients with Autoimmune Diseases and with Dyspepsia: A Follow-up Study.
- Author
-
Sorrentino, U., Ferraccioll, G. F., Devita, S., Labombarda, A., Avellini, C., Ponzetto, A., Beltrami, C. A., Boiocchi, M., and Bartoli, E.
- Published
- 1997
- Full Text
- View/download PDF
6. Inhibition of nitric oxide synthase expression by a methanolic extract of Crescentia alata and its derived flavonols
- Author
-
Autore, G., Rastrelli, L., Lauro, M. R., Marzocco, S., Sorrentino, R., Sorrentino, U., Pinto, A., and Aquino, R.
- Published
- 2001
- Full Text
- View/download PDF
7. Improvement of gliquidone hypoglycaemic effect in rats by cyclodextrin formulations
- Author
-
Raffaella Sorrentino, Agnese Miro, U. Sorrentino, Fabiana Quaglia, R. d’Emmanuele di Villa Bianca, M.I. La Rotonda, Miro, Agnese, Quaglia, Fabiana, Sorrentino, U., LA ROTONDA, MARIA IMMACOLATA, D'EMMANUELE DI VILLA BIANCA, Roberta, and Sorrentino, Raffaella
- Subjects
Dissolution rate ,Blood Glucose ,Male ,animal structures ,Chemical Phenomena ,Chemistry, Pharmaceutical ,Drug Compounding ,Pharmaceutical Science ,Biological Availability ,Inclusion compound ,Excipients ,Hypoglycaemic effect ,chemistry.chemical_compound ,Pharmacokinetics ,X-Ray Diffraction ,Oral administration ,Spectroscopy, Fourier Transform Infrared ,medicine ,Animals ,Hypoglycemic Agents ,rat ,Solubility ,Rats, Wistar ,chemistry.chemical_classification ,Cyclodextrins ,Chromatography ,Aqueous solution ,integumentary system ,Cyclodextrin ,Calorimetry, Differential Scanning ,Chemistry, Physical ,Hydrogen-Ion Concentration ,Bioavailability ,Rats ,Cyclodextrins Complexation ,Freeze Drying ,Sulfonylurea Compounds ,chemistry ,Area Under Curve ,embryonic structures ,Gliquidone ,Algorithms ,medicine.drug - Abstract
This study was carried out with the aim to optimize the pharmacological profile of gliquidone (GLI)--a poorly bioavailable hypoglycaemic agent sparingly soluble in water--through complexation with cyclodextrins. In order to increase the apparent solubility of GLI, two cyclodextrins, namely beta-cyclodextrin (betaCD) and hydroxypropyl-beta-cyclodextrin (HPbetaCD), were tested. The effect of cyclodextrin addition on the aqueous solubility of GLI was evaluated by the phase solubility method at different pH values. The amount of GLI in solution increased upon CD addition according to A type plots. The aqueous solubility of GLI was enhanced more at higher pH values and using HPbetaCD. On the basis of its performance, HPbetaCD was selected as host to prepare GLI oral formulations. GLI/HPbetaCD solid systems were prepared at 1:2 molar ratio by co-grinding, spray-drying and freeze-drying and characterized by DSC, FTIR and X-ray powder diffractometry. Powders were amorphous and showed an improved dissolution rate in comparison with GLI. GLI/HPbetaCD co-ground and freeze-dried products were the most interesting systems, since they dissolved 62 and 94% of total drug after 15 min, respectively. The hypoglycaemic effect of the most rapidly dissolving binary systems was evaluated after oral administration in fasted rats by measuring plasma glucose level in the time interval 0.5-36 h and compared to free GLI. Our findings indicate that cyclodextrin-containing formulations not only provide an onset of hypoglycaemic effect faster than GLI, but also enhance significantly the pharmacological effect due to improved biopharmaceutics. The association GLI/HPbetaCD allows a reduction of the oral dose and is expected to provide a better control over drug side effects, contributing to improve safety and efficacy of GLI.
- Published
- 2003
8. INHIBITION OF NITRIC OXIDE SYNTHASE EXPRESSION BY A METHANOLIC EXTRACT OF CRESCENTIA ALATA AND ITS DERIVED FLAVONOLS
- Author
-
Raffaella Sorrentino, Maria Rosaria Lauro, Aldo Pinto, Ugo Sorrentino, Luca Rastrelli, Giuseppina Autore, Stefania Marzocco, Rita Patrizia Aquino, Autore, G., Rastrelli, L., Lauro, Mr, Marzocco, S., Sorrentino, Raffaella, Sorrentino, U., and Pinto, A. AND AQUINO R.
- Subjects
Male ,Flavonols ,Rutin ,Anti-Inflammatory Agents ,Nitric Oxide Synthase Type II ,Nitric Oxide ,General Biochemistry, Genetics and Molecular Biology ,Nitric oxide ,chemistry.chemical_compound ,In vivo ,Animals ,Edema ,General Pharmacology, Toxicology and Pharmaceutics ,Enzyme Inhibitors ,Kaempferols ,Rats, Wistar ,Cells, Cultured ,chemistry.chemical_classification ,Flavonoids ,biology ,Dose-Response Relationship, Drug ,Plant Extracts ,Macrophages ,General Medicine ,Macrophage Activation ,Hindlimb ,Rats ,Nitric oxide synthase ,Plant Leaves ,Aglycone ,chemistry ,Biochemistry ,Bignoniaceae ,biology.protein ,Quercetin ,Medicine, Traditional ,Nitric Oxide Synthase ,Kaempferol - Abstract
In order to validate the use of Crescentia alata (Bignoniaceae) in the traditional medicine of Guatemala as an antiinflammatory remedy, the methanolic (MeOH) extract has been evaluated in vivo for antiinflammatory activity on carrageenin paw edema in rats and in vitro on Escherichia coli lipopolysaccharide- (LPS)-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in J774.A1 macrophage cell line. This extract exerted in vivo a significant anti-inflammatory activity at the highest dose tested. The same extract showed in vitro an inhibitory activity on inducible nitric oxide synthase expression and on NO formation in LPS-primed J774.A1 cells. Subsequent fractionation and analysis of the extract has led to the isolation and characterization as major constituents of two flavonol glycosides: quercetin 3-O-alpha-L-rhamnopyranosyl-(1->6)-beta-D-glucopyranoside (rutin) 1, kaempferol 3-O-alpha-L-rhamnopyranosyl-(1->6)-beta-D-glucopyranoside (kaempferol 3-O-rutinoside) 2, and flavonol aglycone, kaempferol 3. Their structures were elucidated by spectral methods. The bioassay-directed analysis of flavonols 1-3 indicated that kaempferol (3) was the most active compound contained in the MeOH extract because it reduced in vitro both NO production and iNOS expression in LPS-primed J774.A1 cells, whereas rutin (1) and kaempferol 3-O-rutinoside (2) showed no significant activity. The MeOH extract and all of flavonoids tested did not show in vitro significant cytotoxic effect in J774.A1 macrophage cell line.
- Published
- 2001
9. Characterization of Two Novel PNKP Splice-Site Variants in a Proband With Microcephaly, Intellectual Disability, and Multiple Malformations.
- Author
-
Sorrentino U, Baschiera E, Desbats MA, Zuffardi O, Salviati L, and Cassina M
- Abstract
Polynucleotide kinase phosphatase (PNKP), encoded by the PNKP gene, is a DNA processing enzyme involved in double-strand break and single-strand break repair pathways, which are essential for genome stability and for the correct development and maintenance of human nervous system. PNKP biallelic loss-of-function variants have been associated with a broad spectrum of neurological anomalies, ranging from congenital microcephaly with intellectual disability and seizures (MCSZ), to later onset forms of ataxia-oculomotor apraxia (AOA4) or peripheral neuropathy (CMT2B2). We report the atypical clinical manifestations of a patient with severe microcephaly, short stature, developmental delay, conductive hearing loss, and tracheoesophageal malformation, in the absence of seizures. Whole exome sequencing analysis identified two novel, compound heterozygous splice-site variants in the PNKP gene (NM_007254.4): c.1448+1G > A and c.199-8_199-5del. To demonstrate the effect of both variants on the splicing process and prove their pathogenicity, we performed a hybrid minigene assay, which successfully highlighted a deleterious impact on the transcript, particularly regarding the c.199-8_199-5del variant. The uncommon clinical features of the proband and the identification of two newly associated pathogenic variants add further evidence to the allelic and phenotypic heterogeneity of the PNKP locus., (© 2024 The Author(s). American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)
- Published
- 2024
- Full Text
- View/download PDF
10. Potassium Channel Subunit Kir4.1 Mutated in Paroxysmal Kinesigenic Dyskinesia: Screening of an Italian Cohort.
- Author
-
Zorzi G, Zibordi F, Sorrentino U, Prokisch H, Garavaglia B, and Zech M
- Published
- 2024
- Full Text
- View/download PDF
11. Heterozygosity for loss-of-function variants in LZTR1 is associated with isolated multiple café-au-lait macules.
- Author
-
Mastromoro G, Santoro C, Motta M, Sorrentino U, Daniele P, Peduto C, Petrizzelli F, Tripodi M, Pinna V, Zanobio M, Rotundo G, Bellacchio E, Lepri F, Farina A, D'Asdia MC, Piceci-Sparascio F, Biagini T, Petracca A, Castori M, Melis D, Accadia M, Traficante G, Tarani L, Fontana P, Sirchia F, Paparella R, Currò A, Benedicenti F, Scala I, Dentici ML, Leoni C, Trevisan V, Cecconi A, Giustini S, Pizzuti A, Salviati L, Novelli A, Zampino G, Zenker M, Genuardi M, Digilio MC, Papi L, Perrotta S, Nigro V, Castellanos E, Mazza T, Trevisson E, Tartaglia M, Piluso G, and De Luca A
- Abstract
Purpose: Pathogenic LZTR1 variants cause schwannomatosis and dominant/recessive Noonan syndrome (NS). We aim to establish an association between heterozygous loss-of-function LZTR1 alleles and isolated multiple café-au-lait macules (CaLMs)., Methods: A total of 849 unrelated participants with multiple CaLMs, lacking pathogenic/likely pathogenic NF1 and SPRED1 variants, underwent RASopathy gene panel sequencing. Data on 125 individuals with heterozygous LZTR1 variants were collected for characterizing their clinical features and the associated molecular spectrum. In vitro functional assessment was performed on a representative panel of missense variants and small in-frame deletions., Results: Analysis revealed heterozygous LZTR1 variants in 6.0% (51/849) of participants, exceeding the general population prevalence. LZTR1-related CaLMs varied in number, displayed sharp or irregular borders, and were generally isolated but occasionally associated with features recurring in RASopathies. In 2 families, CaLMs and schwannomas co-occurred. The molecular spectrum mainly consisted of truncating variants, indicating loss-of-function. These variants substantially overlapped with those occurring in schwannomatosis and recessive NS. Functional characterization showed accelerated protein degradation or mislocalization, and failure to downregulate mitogen-activated protein kinase signaling., Conclusion: Our findings expand the phenotypic variability associated with LZTR1 variants, which, in addition to conferring susceptibility to schwannomatosis and causing dominant and recessive NS, occur in individuals with isolated multiple CaLMs., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
12. Pseudodominant inheritance of retinitis pigmentosa in a family with mutations in the Eyes Shut Homolog (EYS) gene.
- Author
-
Di Iorio E, Adamo GG, Sorrentino U, De Nadai K, Barbaro V, Mura M, Pellegrini M, Boaretto F, Tavolato M, Suppiej A, Nasini F, Salviati L, and Parmeggiani F
- Subjects
- Humans, Female, Male, Adult, Middle Aged, High-Throughput Nucleotide Sequencing, Mutation, Frameshift Mutation, Genes, Dominant, Exons genetics, Heterozygote, Retinitis Pigmentosa genetics, Pedigree, Eye Proteins genetics, DNA Copy Number Variations
- Abstract
Sequence variants in Eyes Shut Homolog (EYS) gene are one of the most frequent causes of autosomal recessive retinitis pigmentosa (RP). Herein, we describe an Italian RP family characterized by EYS-related pseudodominant inheritance. The female proband, her brother, and both her sons showed typical RP, with diminished or non-recordable full-field electroretinogram, narrowing of visual field, and variable losses of central vision. To investigate this apparently autosomal dominant pedigree, next generation sequencing (NGS) of a custom panel of RP-related genes was performed, further enhanced by bioinformatic detection of copy-number variations (CNVs). Unexpectedly, all patients had a compound heterozygosity involving two known pathogenic EYS variants i.e., the exon 33 frameshift mutation c.6714delT and the exon 29 deletion c.(5927þ1_5928-1)_(6078þ1_6079-1)del, with the exception of the youngest son who was homozygous for the above-detailed frameshift mutation. No pathologic eye conditions were instead observed in the proband's husband, who was a heterozygous healthy carrier of the same c.6714delT variant in exon 33 of EYS gene. These findings provide evidence that pseudodominant pattern of inheritance can hide an autosomal recessive RP partially or totally due to CNVs, recommending CNVs study in those pedigrees which remain genetically unsolved after the completion of NGS or whole exome sequencing analysis., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
13. Challenges of Preimplantation Genetic Counselling in the Context of Cystic Fibrosis and Other CFTR-Related Disorders: A Monocentric Experience in a Cohort of 92 Couples.
- Author
-
Sorrentino U, Menegazzo M, Gabbiato I, Calosci D, Zambon CF, and Zuccarello D
- Subjects
- Humans, Female, Male, Adult, Retrospective Studies, Pregnancy, Genetic Testing methods, Cystic Fibrosis genetics, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Genetic Counseling, Preimplantation Diagnosis
- Abstract
Cystic fibrosis is a highly prevalent genetic disorder caused by biallelic pathogenic variants in the CFTR gene, causing an altered function of the exocrine glands and a subsequent spectrum of hypofunctional and degenerative manifestations. The increasing availability of carrier screening programmes, the enhanced life expectancy of patients due to improved treatment and care strategies and the development of more precise and affordable molecular diagnostic tools have prompted a rise in demand of prenatal diagnosis procedures for at-risk couples, including Preimplantation Genetic Testing (PGT). However, challenges remain: heterogeneity among screening programmes, nuances of variant interpretation and availability of novel treatments demand a considerate and knowledgeable approach to genetic counselling. In this work, we retrospectively evaluated the molecular data of 92 unselected couples who received a diagnosis of CFTR-related status and were referred to the genetics clinic at the University Hospital of Padua for genetic counselling on eligibility for PGT. A total of 50 couples were considered eligible for the procedure based on risk of transmitting biallelic pathogenic variants. We report and discuss our experience with this case series in the context of the Italian medical care system and present an overview of the most relevant issues regarding genetic counselling for PGT in CFTR-related disorders.
- Published
- 2024
- Full Text
- View/download PDF
14. A yeast based assay establishes the pathogenicity of novel missense ACTA2 variants associated with aortic aneurysms.
- Author
-
Calderan C, Sorrentino U, Persano L, Trevisson E, Sartori G, Salviati L, and Desbats MA
- Subjects
- Humans, Male, Female, Aortic Aneurysm, Thoracic genetics, Aortic Aneurysm, Thoracic pathology, Middle Aged, Heterozygote, Aged, Mitochondria genetics, Actins genetics, Actins metabolism, Mutation, Missense, Saccharomyces cerevisiae genetics
- Abstract
The ACTA2 gene codes for alpha-smooth muscle actin, a critical component of the contractile apparatus of the vascular smooth muscle cells. Autosomal dominant variants in the ACTA2 gene have been associated to familial non-syndromic thoracic aortic aneurysm/dissection (TAAD). They are thought to act through a dominant-negative mechanism. These variants display incomplete penetrance and variable expressivity, complicating the validation of ACTA2 variants pathogenicity by family segregation studies. In this study, we developed a yeast based assay to test putative TAAD-associated ACTA2 variants. We identified five new heterozygous ACTA2 missense variants in TAAD patients through next generation sequencing. We decided to test their pathogenicity in Saccharomyces cerevisiae, since yeast actin is very similar to human alpha-smooth muscle actin, and the residues at which the TAAD-associated variants occur in ACTA2 are well conserved. A wild type yeast strain was transformed with a vector expressing the different mutant alleles, to model the heterozygous condition of patients. Then, we evaluated yeast growth by spot test and cytoskeletal and mitochondrial morphology by fluorescence microscopy. We found that mutant yeast strains displayed only mild growth defects but a significant increase in the percentage of cells with abnormal mitochondrial distribution and abnormal organization of the actin cytoskeleton compared to controls. All variants appeared to interfere with the activity of wild type actin in yeast, suggesting a dominant-negative pathogenic mechanism. Our results demonstrate the utility of using the yeast actin model system to validate the pathogenicity of TAAD-associated ACTA2 variants., (© 2024. The Author(s), under exclusive licence to European Society of Human Genetics.)
- Published
- 2024
- Full Text
- View/download PDF
15. The impact of a second embryo biopsy for preimplantation genetic testing for monogenic diseases (PGT-M) with inconclusive results on pregnancy potential: results from a matched case-control study.
- Author
-
Guarneri C, Reschini M, Pinna M, Perego L, Sanzani E, Somigliana E, Sorrentino U, Cassina M, Zuccarello D, and Ciaffaglione M
- Subjects
- Humans, Biopsy, Embryo Implantation, Genetic Testing, Pregnancy, Adult, Reproductive Techniques, Assisted, Case-Control Studies, Pregnancy Outcome, Infertility, Female, Embryo, Mammalian metabolism
- Abstract
Purpose: To evaluate whether a second biopsy, following a first diagnostic failure on blastocysts tested for preimplantation genetic testing for monogenic diseases (PGT-M), allows to obtain genetic diagnosis and to what extent this procedure can influence clinical pregnancy and live birth rates compared to the PGT-M process with a successful genetic diagnosis from the first biopsy., Methods: Embryos from women who underwent PGT-M in an infertility centre and who had been transferred after two biopsies for genetic analysis (n = 27) were matched in a 1:1 ratio accordingly to women's age (± 1 year) and fertility status (fertile vs infertile), as well as with the study period, with embryos who were transferred after receiving a conclusive PGT result straight after the first biopsy (n = 27). The main evaluated outcome was clinical pregnancy rate following embryo transfers in which healthy embryos were transferred after only one biopsy and those in which an embryo was transferred after being re-biopsied. Live birth rate was the secondary outcome., Results: Clinical pregnancy rate was 52% (95% CI: 34-69) following the transfer of a single-biopsy blastocyst and 30% (95% CI: 16-48) following the transfer of a re-biopsied blastocyst. The likelihood to have a healthy baby was 33% (95% CI: 19-52) following the transfer of a blastocyst biopsied once and 22% (95% CI: 11-41) following the transfer of a re-biopsied blastocyst., Conclusions: The re-biopsy intervention seems to considerably reduce the pregnancy potential of a blastocyst. However, a greater sample size is necessary to clarify this issue definitively., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
- Full Text
- View/download PDF
16. CHD8-related disorders redefined: an expanding spectrum of dystonic phenotypes.
- Author
-
Sorrentino U, Boesch S, Doummar D, Ravelli C, Serranova T, Indelicato E, Winkelmann J, Burglen L, Jech R, and Zech M
- Subjects
- Humans, Female, Dystonia genetics, Dystonia etiology, Dystonia physiopathology, Dystonia diagnosis, Transcription Factors genetics, Child, Adolescent, Neurodevelopmental Disorders genetics, Neurodevelopmental Disorders diagnosis, Adult, Dystonic Disorders genetics, Dystonic Disorders diagnosis, Dystonic Disorders physiopathology, Dystonic Disorders complications, Frameshift Mutation, Young Adult, Child, Preschool, Phenotype, DNA-Binding Proteins genetics
- Abstract
Background: Heterozygous loss-of-function variants in CHD8 have been associated with a syndromic neurodevelopmental-disease spectrum, collectively referred to as CHD8-related neurodevelopmental disorders. Several different clinical manifestations, affecting neurodevelopmental and systemic domains, have been described, presenting with highly variable expressivity. Some expressions are well established and comprise autism spectrum disorders, psychomotor delay with cognitive impairment, postnatal overgrowth with macrocephaly, structural brain abnormalities, gastrointestinal disturbances, and behavioral and sleep-pattern problems. However, the complete phenotypic spectrum of CHD8-related disorders is still undefined. In 2021, our group described two singular female patients with CHD8-related neurodevelopmental disorder and striking dystonic manifestations, prompting the suggestion that dystonia should be considered a possible component of this condition., Case Series Presentation: We describe three additional unrelated female individuals, each carrying a different CHD8 frameshift variant and whose clinical presentations were primarily characterized by young-onset dystonia. Their dystonic manifestations were remarkably heterogeneous and ranged from focal, exercise-dependent, apparently isolated forms to generalized permanent phenotypes accompanied by spasticity and tremor. Neurocognitive impairment and autistic behaviors, typical of CHD8-related disorders, were virtually absent or at the mild end of the spectrum., Conclusions: This work validates our previous observation that dystonia is part of the phenotypic spectrum of CHD8-related neurodevelopmental disorders with potential female preponderance, raising new challenges and opportunities in the diagnosis and management of this condition. It also highlights the importance of in-depth neurologic phenotyping of patients carrying variants associated with neurodevelopmental disorders, as the connection between neurodevelopmental and movement disorders is proving closer than previously appreciated., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
17. Myoclonus and Dystonia as Recurrent Presenting Features in Patients with the SCA21-Associated TMEM240 p.Pro170Leu Variant.
- Author
-
Sorrentino U, Romito LM, Garavaglia B, Fichera M, Colangelo I, Prokisch H, Winkelmann J, Necpal J, Jech R, and Zech M
- Subjects
- Humans, Hyperkinesis, Ataxia, Rare Diseases, Syndrome, Membrane Proteins, Dystonia diagnosis, Dystonia genetics, Myoclonus diagnosis, Myoclonus genetics, Spinocerebellar Degenerations, Dystonic Disorders
- Abstract
Background: Spinocerebellar ataxia 21 (SCA21) is a rare neurological disorder caused by heterozygous variants in TMEM240 . A growing, yet still limited number of reports suggested that hyperkinetic movements should be considered a defining component of the disease., Case Series: We describe two newly identified families harboring the recurrent pathogenic TMEM240 p.Pro170Leu variant. Both index patients and the mother of the first proband developed movement disorders, manifesting as myoclonic dystonia and action-induced dystonia without co-occurring ataxia in one case, and pancerebellar syndrome complicated by action-induced dystonia in the other. We reviewed the literature on TMEM240 variants linked to hyperkinetic disorders, comparing our cases to described phenotypes., Discussion: Adding to prior preliminary observations, our series highlights the relevance of hyperkinetic movements as clinically meaningful features of SCA21. TMEM240 mutation should be included in the differential diagnosis of myoclonic dystonia and ataxia-dystonia syndromes., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
18. ZFHX4 truncating variant and orofacial clefting.
- Author
-
Sorrentino U, Fedrigo M, Calò AP, Perin M, Veronese P, and Salviati L
- Subjects
- Humans, Transcription Factors, Homeodomain Proteins, Cleft Palate diagnosis, Cleft Palate genetics, Cleft Lip diagnosis, Cleft Lip genetics
- Published
- 2024
- Full Text
- View/download PDF
19. PGT-M for Premature Ovarian Failure Related to CGG Repeat Expansion of the FMR1 Gene.
- Author
-
Persico T, Tranquillo ML, Seracchioli R, Zuccarello D, and Sorrentino U
- Subjects
- Female, Humans, 5' Untranslated Regions, Alleles, Fragile X Mental Retardation Protein genetics, Genetic Testing, Mutation, Fragile X Syndrome genetics, Primary Ovarian Insufficiency genetics
- Abstract
Primary ovarian failure (POF) is caused by follicle exhaustion and is associated with menstrual irregularities and elevated gonadotropin levels, which lead to infertility before the age of 40 years. The etiology of POI is mostly unknown, but a heterogeneous genetic and familial background can be identified in a subset of cases. Abnormalities in the fragile X mental retardation 1 gene ( FMR1 ) are among the most prevalent monogenic causes of POI. These abnormalities are caused by the expansion of an unstable CGG repeat in the 5' untranslated region of FMR1 . Expansions over 200 repeats cause fragile X syndrome (FXS), whereas expansions between 55 and 200 CGG repeats, which are defined as a fragile X premutation, have been associated with premature ovarian failure type 1 (POF1) in heterozygous females. Preimplantation genetic testing for monogenic diseases (PGT-M) can be proposed when the female carries a premutation or a full mutation. In this narrative review, we aim to recapitulate the clinical and molecular features of POF1 and their implications in the context of PGT-M.
- Published
- 2023
- Full Text
- View/download PDF
20. Preimplantation Genetic Testing for Genetic Diseases: Limits and Review of Current Literature.
- Author
-
Giuliano R, Maione A, Vallefuoco A, Sorrentino U, and Zuccarello D
- Subjects
- Pregnancy, Female, Humans, Genetic Testing methods, Preimplantation Diagnosis methods
- Abstract
Preimplantation genetic testing (PGT) has emerged as a revolutionary technique in the field of reproductive medicine, allowing for the selection and transfer of healthy embryos, thus reducing the risk of transmitting genetic diseases. However, despite remarkable advancements, the implementation of PGT faces a series of limitations and challenges that require careful consideration. This review aims to foster a comprehensive reflection on the constraints of preimplantation genetic diagnosis, encouraging a broader discussion about its utility and implications. The objective is to inform and guide medical professionals, patients, and society overall in the conscious and responsible adoption of this innovative technology, taking into account its potential benefits and the ethical and practical challenges that it presents., Competing Interests: The authors declare no conflict of interest.
- Published
- 2023
- Full Text
- View/download PDF
21. Public Awareness and Acceptability of PGT-M in Cancer Predisposition Syndromes.
- Author
-
Calosci D, Passaglia L, Gabbiato I, Cartisano F, Affuso R, Sorrentino U, and Zuccarello D
- Subjects
- Pregnancy, Female, Humans, Genetic Testing methods, Reproduction, Disease Susceptibility, Preimplantation Diagnosis methods, Neoplasms diagnosis, Neoplasms genetics
- Abstract
Cancer Predisposition Syndromes (CPSs), also known as Hereditary Cancer Syndromes (HCSs), represent a group of genetic disorders associated with an increased lifetime risk of developing cancer. In this article, we provide an overview of the reproductive options for patients diagnosed with CPS, focusing on the emerging role of Preimplantation Genetic Testing for Monogenic disorders (PGT-M). Specifically, we conducted a literature review about the awareness and acceptability of its application to CPSs. Based on the available data, the awareness of the applicability of PGT-M for CPSs appears to be limited among both patients and physicians, and a heterogeneous set of factors seems to influence the acceptability of the procedure. Our findings highlight the need for increasing education about the use of PGT-M for CPSs. In this context, guidelines developed by professional or institutional bodies would represent a useful reference tool to assist healthcare professionals in providing proper preconception counseling.
- Published
- 2023
- Full Text
- View/download PDF
22. Severe trichothiodystrophy and cardiac malformation in a newborn carrying a novel GTF2H5 homozygous truncating variant.
- Author
-
Sorrentino U, Agosto C, Benini F, Bertolin C, Cassina M, Bonadies L, Caroppo F, Fortina AB, and Salviati L
- Subjects
- Humans, Infant, Newborn, Male, Homozygote, Phenotype, Transcription Factors genetics, Trichothiodystrophy Syndromes genetics
- Abstract
We report a newborn patient with trichothiodystrophy-3 (TTD3) caused by a novel homozygous variant in the GTF2H5 gene. His severe phenotype included congenital ichthyosis, complex posterior cranial fossa anomaly, life-threatening infections, bilateral cryptorchidism, and, notably, a complex cardiac malformation, which is unprecedented in TTD3 patients., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
23. Homozygous TNNI3 Mutations and Severe Early Onset Dilated Cardiomyopathy: Patient Report and Review of the Literature.
- Author
-
Sorrentino U, Gabbiato I, Canciani C, Calosci D, Rigon C, Zuccarello D, and Cassina M
- Subjects
- Humans, Homozygote, Mutation, Myocardium, Troponin I genetics, Cardiomyopathy, Dilated genetics
- Abstract
The TNNI3 gene encodes for the cardiac isoform of troponin I, a pivotal component of the sarcomeric structure of the myocardium. While heterozygous TNNI3 missense mutations have long been associated with autosomal dominant hypertrophic and restrictive cardiomyopathies, the role of TNNI3 null mutations has been more debated due to the paucity and weak characterization of reported cases and the low penetrance of heterozygous genotypes. In recent years, however, an increasing amount of evidence has validated the hypothesis that biallelic TNNI3 null mutations cause a severe form of neonatal dilated cardiomyopathy. Here, we expand the case series reporting two unrelated patients afflicted with early onset dilated cardiomyopathy, due to homozygosity for the p.Arg98* TNNI3 variant, which had thus far been documented only in heterozygous patients and apparently healthy carriers, and the recurrent p.Arg69Alafs*8 variant, respectively. A review of previously reported biallelic TNNI3 loss-of-function variants and their associated cardiac phenotypes was also performed.
- Published
- 2023
- Full Text
- View/download PDF
24. Epigenetics of pregnancy: looking beyond the DNA code.
- Author
-
Zuccarello D, Sorrentino U, Brasson V, Marin L, Piccolo C, Capalbo A, Andrisani A, and Cassina M
- Subjects
- Adult, DNA metabolism, Female, Fetus metabolism, Humans, Pregnancy, Epigenesis, Genetic genetics, Fetal Development genetics
- Abstract
Epigenetics is the branch of genetics that studies the different mechanisms that influence gene expression without direct modification of the DNA sequence. An ever-increasing amount of evidence suggests that such regulatory processes may play a pivotal role both in the initiation of pregnancy and in the later processes of embryonic and fetal development, thus determining long-term effects even in adult life. In this narrative review, we summarize the current knowledge on the role of epigenetics in pregnancy, from its most studied and well-known mechanisms to the new frontiers of epigenetic regulation, such as the role of ncRNAs and the effects of the gestational environment on fetal brain development. Epigenetic mechanisms in pregnancy are a dynamic phenomenon that responds both to maternal-fetal and environmental factors, which can influence and modify the embryo-fetal development during the various gestational phases. Therefore, we also recapitulate the effects of the most notable environmental factors that can affect pregnancy and prenatal development, such as maternal nutrition, stress hormones, microbiome, and teratogens, focusing on their ability to cause epigenetic modifications in the gestational environment and ultimately in the fetus. Despite the promising advancements in the knowledge of epigenetics in pregnancy, more experience and data on this topic are still needed. A better understanding of epigenetic regulation in pregnancy could in fact prove valuable towards a better management of both physiological pregnancies and assisted reproduction treatments, other than allowing to better comprehend the origin of multifactorial pathological conditions such as neurodevelopmental disorders., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
25. Epilepsy in NF1: Epidemiologic, Genetic, and Clinical Features. A Monocentric Retrospective Study in a Cohort of 784 Patients.
- Author
-
Sorrentino U, Bellonzi S, Mozzato C, Brasson V, Toldo I, Parrozzani R, Clementi M, Cassina M, and Trevisson E
- Abstract
An increased lifetime risk of epilepsy has been reported in neurofibromatosis type 1 (NF1) patients, ranging between 4% and 14%. To further analyze the correlation between NF1 and epilepsy, we retrospectively reviewed the epidemiologic, clinical, radiological, and molecular data of 784 unselected patients diagnosed with NF1 and referred to the neurofibromatosis outpatient clinics at the University Hospital of Padua. A crude prevalence of epilepsy of 4.7% was observed. In about 70% of cases, seizures arose in the context of neuroradiological findings, with the main predisposing factors being cerebral vasculopathies and hydrocephalus. In the absence of structural abnormalities, the prevalence of epilepsy was found to be 1.27%, which is approximately equal to the total prevalence in the general population. NF1 patients with seizures exhibit a higher incidence of intellectual disability and/or developmental delay, as well as of isolated learning disabilities. The comparison of causative NF1 mutations between the two groups did not reveal a specific genotype-phenotype correlation. Our data refine the current knowledge on epileptological manifestations in NF1 patients, arguing against the hypothesis that specific mechanisms, inherent to neurofibromin cellular function, might determine an increased risk of epilepsy in this condition.
- Published
- 2021
- Full Text
- View/download PDF
26. Genetics & Epigenetics of Hereditary Deafness: An Historical Overview.
- Author
-
Martini A, Sorrentino F, Sorrentino U, and Cassina M
- Abstract
Hearing loss (HL) is one of the most common sensory impairments worldwide and represents a critical medical and public health issue. Since the mid-1900s, great efforts have been aimed at understanding the etiology of both syndromic and non-syndromic HL and identifying correlations with specific audiological phenotypes. The extraordinary discoveries in the field of molecular genetics during the last three decades have contributed substantially to the current knowledge. Next-generation sequencing technologies have dramatically increased the diagnostic rate for genetic HL, enabling the detection of novel variants in known deafness-related genes and the discovery of new genes implicated in hearing disease. Overall, genetic factors account for at least 40% of the cases with HL, but a portion of affected patients still lack a definite molecular diagnosis. Important steps forward have been made, but many aspects still have to be clarified. In particular, the role of epigenetics in the development, function and pathology of hearing is a research field that still needs to be explored. This research is extremely challenging due to the time- and tissue-dependent variability of the epigenetic changes. Multisystem diseases are expected to be investigated at first: specific epi-signatures have been identified for several syndromic disorders and represent potential markers for molecular diagnostics.
- Published
- 2021
- Full Text
- View/download PDF
27. DFNA20/26 and Other ACTG1-Associated Phenotypes: A Case Report and Review of the Literature.
- Author
-
Sorrentino U, Piccolo C, Rigon C, Brasson V, Trevisson E, Boaretto F, Martini A, and Cassina M
- Abstract
Since the early 2000s, an ever-increasing subset of missense pathogenic variants in the ACTG1 gene has been associated with an autosomal-dominant, progressive, typically post-lingual non-syndromic hearing loss (NSHL) condition designed as DFNA20/26. ACTG1 gene encodes gamma actin, the predominant actin protein in the cytoskeleton of auditory hair cells; its normal expression and function are essential for the stereocilia maintenance. Different gain-of-function pathogenic variants of ACTG1 have been associated with two major phenotypes: DFNA20/26 and Baraitser-Winter syndrome, a multiple congenital anomaly disorder. Here, we report a novel ACTG1 variant [c.625G>A (p. Val209Met)] in an adult patient with moderate-severe NSHL characterized by a downsloping audiogram. The patient, who had a clinical history of slowly progressive NSHL and tinnitus, was referred to our laboratory for the analysis of a large panel of NSHL-associated genes by next generation sequencing. An extensive review of previously reported ACTG1 variants and their associated phenotypes was also performed.
- Published
- 2021
- Full Text
- View/download PDF
28. The multiple roles of coenzyme Q in cellular homeostasis and their relevance for the pathogenesis of coenzyme Q deficiency.
- Author
-
Baschiera E, Sorrentino U, Calderan C, Desbats MA, and Salviati L
- Subjects
- Ataxia, Homeostasis, Humans, Muscle Weakness, Mitochondrial Diseases genetics, Ubiquinone deficiency
- Abstract
Coenzyme Q (CoQ) is a redox active lipid that plays a central role in cellular homeostasis. It was discovered more than 60 years ago because of its role as electron transporter in the mitochondrial respiratory chain. Since then it has become evident that CoQ has many other functions, not directly related to bioenergetics. It is a cofactor of several mitochondrial dehydrogenases involved in the metabolism of lipids, amino acids, and nucleotides, and in sulfide detoxification. It is a powerful antioxidant and it is involved in the control of programmed cell death by modulating both apoptosis and ferroptosis. CoQ deficiency is a clinically and genetically heterogeneous group of disorders characterized by the impairment of CoQ biosynthesis. CoQ deficient patients display defects in cellular bioenergetics, but also in the other pathways in which CoQ is involved. In this review we will focus on the functions of CoQ not directly related to the respiratory chain, and on how their impairment is relevant for the pathophysiology of CoQ deficiency. A better understanding of the complex set of events triggered by CoQ deficiency will allow to design novel approaches for the treatment of this condition., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
- Full Text
- View/download PDF
29. Optic Pathway Glioma in Type 1 Neurofibromatosis: Review of Its Pathogenesis, Diagnostic Assessment, and Treatment Recommendations.
- Author
-
Cassina M, Frizziero L, Opocher E, Parrozzani R, Sorrentino U, Viscardi E, Miglionico G, Midena E, Clementi M, and Trevisson E
- Abstract
Type 1 neurofibromatosis (NF1) is a dominantly inherited condition predisposing to tumor development. Optic pathway glioma (OPG) is the most frequent central nervous system tumor in children with NF1, affecting approximately 15-20% of patients. The lack of well-established prognostic markers and the wide clinical variability with respect to tumor progression and visual outcome make the clinical management of these tumors challenging, with significant differences among distinct centers. We reviewed published articles on OPG diagnostic protocol, follow-up and treatment in NF1. Cohorts of NF1 children with OPG reported in the literature and patients prospectively collected in our center were analyzed with regard to clinical data, tumor anatomical site, diagnostic workflow, treatment and outcome. In addition, we discussed the recent findings on the pathophysiology of OPG development in NF1. This review provides a comprehensive overview about the clinical management of NF1-associated OPG, focusing on the most recent advances from preclinical studies with genetically engineered models and the ongoing clinical trials.
- Published
- 2019
- Full Text
- View/download PDF
30. Carcinoma of eyelid sebaceous glands: a case report.
- Author
-
Leotta A, Lio SG, Caparello B, Sorrentino S, and Sorrentino U
- Subjects
- Adenocarcinoma, Sebaceous diagnosis, Adenocarcinoma, Sebaceous surgery, Aged, 80 and over, Corneal Opacity complications, Corneal Opacity surgery, Eye Enucleation, Female, Granuloma diagnosis, Humans, Iris Diseases etiology, Iris Diseases surgery, Postoperative Complications diagnosis, Postoperative Complications pathology, Postoperative Complications surgery, Sebaceous Gland Neoplasms diagnosis, Sebaceous Gland Neoplasms surgery, Adenocarcinoma, Sebaceous pathology, Diagnostic Errors, Sebaceous Gland Neoplasms pathology
- Abstract
The authors present a case of a rare tumour of the eyelid sebaceous glands with an unfavourable prognosis, and emphasize the importance of carrying out histological examination of all eyelid neoformations to better identify the lesion and obtain an accurate diagnosis. The Authors discuss the histopathologic aspects of this case, and the findings in the literature.
- Published
- 2008
31. Optic neuritis caused by ethembutol.
- Author
-
Erpici M and Sorrentino U
- Subjects
- Ethambutol therapeutic use, Humans, Tuberculosis drug therapy, Ethambutol adverse effects, Optic Neuritis chemically induced
- Published
- 1977
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.