43 results on '"Bruno, Claudio"'
Search Results
2. Risdiplam in Patients Previously Treated with Other Therapies for Spinal Muscular Atrophy: An Interim Analysis from the JEWELFISH Study.
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Chiriboga, Claudia A., Bruno, Claudio, Duong, Tina, Fischer, Dirk, Mercuri, Eugenio, Kirschner, Janbernd, Kostera-Pruszczyk, Anna, Jaber, Birgit, Gorni, Ksenija, Kletzl, Heidemarie, Carruthers, Imogen, Martin, Carmen, Warren, Francis, Scalco, Renata S., Wagner, Kathryn R., and Muntoni, Francesco
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SPINAL muscular atrophy , *RESPIRATORY infections - Abstract
Introduction: Risdiplam is a survival of motor neuron 2 (SMN2) splicing modifier for the treatment of patients with spinal muscular atrophy (SMA). The JEWELFISH study (NCT03032172) was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of risdiplam in previously treated pediatric and adult patients with types 1–3 SMA. Here, an analysis was performed after all patients had received at least 1 year of treatment with risdiplam. Methods: Patients with a confirmed diagnosis of 5q-autosomal recessive SMA between the ages of 6 months and 60 years were eligible for enrollment. Patients were previously enrolled in the MOONFISH study (NCT02240355) with splicing modifier RG7800 or treated with olesoxime, nusinersen, or onasemnogene abeparvovec. The primary objectives of the JEWELFISH study were to evaluate the safety and tolerability of risdiplam and investigate the PK after 2 years of treatment. Results: A total of 174 patients enrolled: MOONFISH study (n = 13), olesoxime (n = 71 patients), nusinersen (n = 76), onasemnogene abeparvovec (n = 14). Most patients (78%) had three SMN2 copies. The median age and weight of patients at enrollment was 14.0 years (1–60 years) and 39.1 kg (9.2–108.9 kg), respectively. About 63% of patients aged 2–60 years had a baseline total score of less than 10 on the Hammersmith Functional Motor Scale–Expanded and 83% had scoliosis. The most common adverse event (AE) was upper respiratory tract infection and pyrexia (30 patients each; 17%). Pneumonia (four patients; 2%) was the most frequently reported serious AE (SAE). The rates of AEs and SAEs per 100 patient-years were lower in the second 6-month period compared with the first. An increase in SMN protein was observed in blood after risdiplam treatment and was comparable across all ages and body weight quartiles. Conclusions: The safety and PD of risdiplam in patients who were previously treated were consistent with those of treatment-naïve patients. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Genetic modifiers of upper limb function in Duchenne muscular dystrophy.
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Sabbatini, Daniele, Fusto, Aurora, Vianello, Sara, Villa, Matteo, Janik, Joanna, D'Angelo, Grazia, Diella, Eleonora, Magri, Francesca, Comi, Giacomo P., Panicucci, Chiara, Bruno, Claudio, D'Amico, Adele, Bertini, Enrico, Astrea, Guja, Battini, Roberta, Politano, Luisa, Masson, Riccardo, Baranello, Giovanni, Previtali, Stefano C., and Messina, Sonia
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DUCHENNE muscular dystrophy ,GENERALIZED estimating equations ,DELAYED onset of disease ,EXPERIMENTAL design ,GENETIC variation - Abstract
Genetic modifiers of Duchenne muscular dystrophy (DMD) are variants located in genes different from the disease-causing gene DMD, but associated with differences in disease onset, progression, or response to treatment. Modifiers described so far have been tested mainly for associations with ambulatory function, while their effect on upper limb function, which is especially relevant for quality of life and independence in non-ambulatory patients, is unknown. We tested genotypes at several known modifier loci (SPP1, LTBP4, CD40, ACTN3) for association with Performance Upper Limb version 1.2 score in an Italian multicenter cohort, and with Brooke scale score in the Cooperative International Neuromuscular Group Duchenne Natural History Study (CINRG-DNHS), using generalized estimating equation (GEE) models of longitudinally collected data, with age and glucocorticoid treatment as covariates. CD40 rs1883832, previously linked to earlier loss of ambulation, emerged as a modifier of upper limb function, negatively affecting shoulder and distal domains of PUL (p = 0.023 and 0.018, respectively) in the Italian cohort, as well as of Brooke score (p = 0.018) in the CINRG-DNHS. These findings will be useful for the design and interpretation of clinical trials in DMD, especially for non-ambulatory populations. [ABSTRACT FROM AUTHOR]
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- 2022
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4. Body mass index in type 2 spinal muscular atrophy: a longitudinal study.
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Ferrantini, Gloria, Coratti, Giorgia, Onesimo, Roberta, Lucibello, Simona, Bompard, Sarah, Turrini, Ida, Cicala, Graziamaria, Caprarelli, Michela, Pera, Maria Carmela, Bravetti, Chiara, Berti, Beatrice, Giorgio, Valentina, Bruno, Claudio, Brolatti, Noemi, Panicucci, Chiara, D'Amico, Adele, Longo, Antonella, Leoni, Chiara, Sansone, Valeria A., and Albamonte, Emilio
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BODY mass index ,NEWBORN infants ,SPINAL muscular atrophy ,NUTRITIONAL status ,MOTOR ability - Abstract
The aim of this retrospective study was to review body mass index (BMI) in a large cohort of Italian pediatric type 2 spinal muscular atrophy (SMA) patients, aged between 0 and 20 years and to establish possible differences in relation to a number of variables such as ventilation, motor function, and survival motor neuron 2 gene copies. Cross-sectional data were collected from 102 patients for a total of 344 visits. Standard growth charts for height and weight were used as reference, with age adjusted BMI calculated using the Center for Disease and Prevention Children's BMI Tool. In the 344 visits, weight ranged between 3.90 and 83 kg, and the BMI between 8.4 and 31.6 with a BMI/age z-scores < − 2SD present in 28% and BMI/age z-scores > + 2SD in 9% of the measurements. The BMI/age z-scores were relatively stable < 5 years of age with an increasing number of patients < − 2SD after the age of 5, and a wider range of BMI/age z-scores after the age of 13. A difference on the BMI/age z-scores was found among the different age subgroups (< 5, 5–12, ≥ 13 years). A multivariate analysis in 58 patients with longitudinal assessments showed that baseline BMI/age z-scores and gender were significantly contributing to the changes while other variables were not. Conclusion: Our results confirm that careful surveillance of weight and BMI/age z-scores is needed in type 2 SMA. Further studies, including assessments of chewing and swallowing and of lean/fat body mass, will help to better understand the possible mechanisms underlying weight issues. What is Known: • Feeding difficulties have been reported in a few studies and were invariably found in patients with type 1 SMA. • Type 2 SMA patients often have low BMI with a relevant number of patients requiring tube feeding. What is New: • Reduction in BMI/age z-score overtime appeared to depend on baseline BMI/age z-score and gender. • Patients with a low BMI/age z-score were at higher risk of developing further reduction. [ABSTRACT FROM AUTHOR]
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- 2022
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5. Kearns-Sayre syndrome: expanding spectrum of a "novel" mitochondrial leukomyeloencephalopathy.
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Moscatelli, Marco, Ardissone, Anna, Lamantea, Eleonora, Zorzi, Giovanna, Bruno, Claudio, Moroni, Isabella, Erbetta, Alessandra, and Chiapparini, Luisa
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Kearns-Sayre syndrome (KSS) is a rare mitochondrial disease associated to a widespread cerebral leukodystrophy. MRI shows a typical centripetal pattern where U-fibers are mainly affected with a relative spare of periventricular white matter. Recently, different patterns of spinal cord involvement have been described in KSS. Here we report 4 new cases with typical cerebral leukodystrophy associated with spinal cord lesions. A pattern characterized by abnormal signal intensity in the H gray matter and posterior columns was found in 2 patients, while the remaining 2 presented a peculiar involvement of the spinal trigeminal nuclei at the junction of low medulla and cervical cord. MRI spinal cord involvement in KSS is probably an underestimated finding and should be evaluated in the diagnostic work up of these patients. [ABSTRACT FROM AUTHOR]
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- 2022
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6. Novel homozygous TSFM pathogenic variant associated with encephalocardiomyopathy with sensorineural hearing loss and peculiar neuroradiologic findings.
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Scala, Marcello, Brigati, Giorgia, Fiorillo, Chiara, Nesti, Claudia, Rubegni, Anna, Pedemonte, Marina, Bruno, Claudio, Severino, Mariasavina, Derchi, Maria, Minetti, Carlo, and Santorelli, F. M.
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SENSORINEURAL hearing loss ,CARDIOMYOPATHIES ,MITOCHONDRIAL pathology ,MATHEMATICAL complexes ,NEURODEGENERATION ,NATURAL history - Abstract
TSFM is a nuclear gene encoding the elongation factor Ts (EFTs), an essential component of mitochondrial translational machinery. Impaired mitochondrial translation is responsible for neurodegenerative disorders characterized by multiple respiratory chain complex defects, multisystemic involvement, and neuroradiological features of Leigh-like syndrome. With the use of a next-generation sequencing (NGS)–based multigene panel for mitochondrial disorders, we identified the novel TSFM homozygous variant c.547G>A (p.Gly183Ser) in a 5-year-old boy with infantile early onset encephalocardiomyopathy, sensorineural hearing loss, and peculiar partially reversible neuroimaging features. Our findings expand the phenotypic spectrum of TSFM-related encephalopathy, offering new insights into the natural history of brain involvement and suggesting that TSFM should be investigated in pediatric mitochondrial disorders with distinctive neurologic and cardiac involvement. [ABSTRACT FROM AUTHOR]
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- 2019
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7. The Crystal Structure of N-[(2E)-3-(4-Chlorophenyl)prop-2-en-1-yl]-4-methoxy-N-methylbenzenesulfonamide.
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Carrozzini, Benedetta, Belviso, Benny Danilo, Bruno, Claudio, Cavalluzzi, Maria Maddalena, Lovece, Angelo, Lentini, Giovanni, and Caliandro, Rocco
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MONOCLINIC crystal system ,CRYSTAL structure ,UNIT cell ,SPACE groups ,PROTEIN kinases - Abstract
The title compound C
17 H18 ClNO3 S crystallizes in the monoclinic P21 /c space group with unit cell parameters a = 15.040 (3) Å, b = 9.151 (6) Å, c = 13.868 (7) Å, β = 116.38 (5)°. Chlorophenyl and methoxyphenyl ring planes are approximately perpendicular and the two moieties form an angle of 82.2°. The crystal packing is stabilized by π–π and Cl–π interactions, which occur between parallel methoxyphenyl and chlorophenyl moieties. Dipolar intermolecular contacts, mainly involving the oxygen atoms and C–H, also contribute to the crystal network. The title compound is formed in the synthetic route for the production of potent inhibitors of calmodulin. Its crystal structure shows the chlorophenyl and methoxyphenyl moieties forming an angle of 82.2°. The crystal packing is stabilized by π–π, Cl–π and dipolar intermolecular contacts. [ABSTRACT FROM AUTHOR]- Published
- 2019
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8. Italian recommendations for diagnosis and management of congenital myasthenic syndromes.
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Maggi, Lorenzo, Bernasconi, Pia, D'Amico, Adele, Brugnoni, Raffaella, Fiorillo, Chiara, Garibaldi, Matteo, Astrea, Guja, Bruno, Claudio, Santorelli, Filippo Maria, Liguori, Rocco, Antonini, Giovanni, Evoli, Amelia, Bertini, Enrico, Rodolico, Carmelo, and Mantegazza, Renato
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CONGENITAL myasthenic syndromes ,GENETIC disorders ,NEUROMUSCULAR diseases ,MYONEURAL junction ,MYASTHENIA gravis ,DIFFERENTIAL diagnosis ,MYASTHENIA gravis treatment ,HEALTH planning ,DISEASE management - Abstract
Congenital myasthenic syndromes (CMS) are genetic disorders due to mutations in genes encoding proteins involved in the neuromuscular junction structure and function. CMS usually present in young children, but perinatal and adult onset has been reported. Clinical presentation is highly heterogeneous, ranging from mild symptoms to severe manifestations, sometimes with life-threatening respiratory episodes, especially in the first decade of life. Although considered rare, CMS are probably underestimated due to diagnostic difficulties. Because of the several therapeutic opportunities, CMS should be always considered in the differential diagnosis of neuromuscular disorders. The Italian Network on CMS proposes here recommendations for proper CMS diagnosis and management, aiming to guide clinicians in their practical approach to CMS patients. [ABSTRACT FROM AUTHOR]
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- 2019
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9. Unusual white matter involvement in EAST syndrome associated with novel KCNJ10 mutations.
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Severino, Mariasavina, Lualdi, Susanna, Fiorillo, Chiara, Striano, Pasquale, De Toni, Teresa, Peluso, Silvio, De Michele, Giuseppe, Rossi, Andrea, Filocamo, Mirella, and Bruno, Claudio
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EPILEPSY ,ATAXIA ,DEAFNESS ,GENETIC mutation ,MAGNETIC resonance imaging of the brain ,DENTATE nucleus ,DISEASE progression - Abstract
Background: Epilepsy, ataxia, sensorineural deafness, and tubulopathy (EAST syndrome) is a rare channelopathy due to KCNJ10 mutations. So far, only mild cerebellar hypoplasia and/or dentate nuclei abnormalities have been reported as major neuroimaging findings in these patients.Methods: We analyzed the clinical and brain MRI features of two unrelated patients (aged 27 and 23 years) with EAST syndrome carrying novel homozygous frameshift mutations (p.Asn232Glnfs*14and p.Gly275Valfs*7) in KCNJ10, detected by whole exome sequencing.Results: Brain MRI examinations at 8 years in Patient 1 and at 13 years in Patient 2 revealed a peculiar brain and spinal cord involvement characterized by restricted diffusion of globi pallidi, thalami, brainstem, dentate nuclei, and cervical spinal cord in keeping with intramyelinic edema. The follow-up studies, performed, respectively, after 19 and 10 years, showed mild cerebellar atrophy and slight progression of the brain and spinal cord T2 signal abnormalities with increase of the restricted diffusion in the affected regions.Conclusion: The present cases harboring novel homozygous frameshift mutations in KCNJ10 expand the spectrum of brain abnormalities in EAST syndrome, including mild cerebellar atrophy and intramyelinic edema, resulting from abnormal function of the Kir4.1 inwardly rectifying potassium channel at the astrocyte endfeet, with disruption of water-ion homeostasis. [ABSTRACT FROM AUTHOR]
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- 2018
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10. Muscle MRI in neutral lipid storage disease (NLSD).
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Garibaldi, Matteo, Tasca, Giorgio, Diaz-Manera, Jordi, Ottaviani, Pierfancesco, Laschena, Francesco, Pantoli, Donatella, Gerevini, Simonetta, Fiorillo, Chiara, Maggi, Lorenzo, Tasca, Elisabetta, D'amico, Adele, Musumeci, Olimpia, Toscano, Antonio, Bruno, Claudio, Massa, Roberto, Angelini, Corrado, Bertini, Enrico, Antonini, Giovanni, and Pennisi, Elena
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DORFMAN-Chanarin syndrome ,MAGNETIC resonance imaging ,GLUTEUS minimus ,SKELETAL muscle ,STERNOCLEIDOMASTOID muscle ,LIPIDOSES ,DIAGNOSIS ,DISEASES - Abstract
Neutral lipid storage disease (NLSD) is a rare inherited disorder of lipid metabolism resulting in lipid droplets accumulation in different tissues. Skeletal muscle could be affected in both two different form of disease: NLSD with myopathy (NLSD-M) and NLSD with ichthyosis (NLSD-I). We present the muscle imaging data of 12 patients from the Italian Network for NLSD: ten patients presenting NLSD-M and two patients with NLSD-I. In NLSD-M gluteus minimus, semimembranosus, soleus and gastrocnemius medialis in the lower limbs and infraspinatus in the upper limbs were the most affected muscles. Gracilis, sartorius, subscapularis, pectoralis, triceps brachii and sternocleidomastoid were spared. Muscle involvement was not homogenous and characteristic 'patchy' replacement was observed in at least one muscle in all the patients. Half of the patients showed one or more STIR positive muscles. In both NLSD-I cases muscle involvement was not observed by T1-TSE sequences, but one of them showed positive STIR images in more than one muscle in the leg. Our data provides evidence that muscle imaging can identify characteristic alterations in NLSD-M, characterized by a specific pattern of muscle involvement with 'patchy' areas of fatty replacement. Larger cohorts are needed to assess if a distinct pattern of muscle involvement exists also for NLSD-I. [ABSTRACT FROM AUTHOR]
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- 2017
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11. Correction to: Kearns‑Sayre syndrome: expanding spectrum of a "novel" mitochondrial leukomyeloencephalopathy.
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Moscatelli, Marco, Ardissone, Anna, Lamantea, Eleonora, Zorzi, Giovanna, Bruno, Claudio, Moroni, Isabella, Erbetta, Alessandra, and Chiapparini, Luisa
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MITOCHONDRIA ,SYNDROMES ,PERSONAL names - Abstract
Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. The original article can be found online at https://doi.org/10.1007/s10072-022-05881-8. Correction to: Kearns-Sayre syndrome: expanding spectrum of a "novel" mitochondrial leukomyeloencephalopathy. [Extracted from the article]
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- 2022
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12. Expanding the Clinical and Magnetic Resonance Spectrum of Leukoencephalopathy with Thalamus and Brainstem Involvement and High Lactate (LTBL) in a Patient Harboring a Novel EARS2 Mutation.
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Biancheri, Roberta, Lamantea, Eleonora, Severino, Mariasavina, Diodato, Daria, Pedemonte, Marina, Cassandrini, Denise, Ploederl, Alexandra, Trucco, Federica, Fiorillo, Chiara, Minetti, Carlo, Santorelli, Filippo M., Zeviani, Massimo, and Bruno, Claudio
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- 2015
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13. New Mutations in NEB Gene Discovered by Targeted Next-Generation Sequencing in Nemaline Myopathy Italian Patients.
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Piga, Daniela, Magri, Francesca, Ronchi, Dario, Corti, Stefania, Cassandrini, Denise, Mercuri, Eugenio, Tasca, Giorgio, Bertini, Enrico, Fattori, Fabiana, Toscano, Antonio, Messina, Sonia, Moroni, Isabella, Mora, Marina, Moggio, Maurizio, Colombo, Irene, Giugliano, Teresa, Pane, Marika, Fiorillo, Chiara, D'Amico, Adele, and Bruno, Claudio
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Nemaline myopathy represents a group of clinically and genetically heterogeneous neuromuscular disorders. Different clinical-genetic entities have been characterized in the last few years, with implications for diagnostics and genetic counseling. Fifty percent of nemaline myopathy forms are due to NEB mutations, but genetic analysis of this large and complex gene by Sanger sequencing is time consuming and expensive. We selected 10 Italian patients with clinical and biopsy features suggestive for nemaline myopathy and negative for ACTA1, TPM2 and TPM3 mutations. We applied a targeted next-generation sequencing strategy designed to analyse NEB coding regions, the relative full introns and the promoter. We also evaluated copy number variations (by CGH array) and transcriptional changes by RNA Sanger sequencing, whenever possible. This combined strategy revealed 11 likely pathogenic variants in 8 of 10 patients. The molecular diagnosis was fully achieved in 3 of 8 patients, while only one heterozygous mutation was observed in 5 subjects. This approach revealed to be a fast and cost-effective way to analyse the large NEB gene in a small group of patients and might be promising for the detection of pathological variants of other genes featuring large coding regions and lacking mutational hotspots. [ABSTRACT FROM AUTHOR]
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- 2016
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14. Spacecraft Propulsion.
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Bruno, Claudio
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- 2014
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15. Bone age assessment with conventional ultrasonography in healthy infants from 1 to 24 months of age.
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Daneff, Monica, Casalis, Claudia, Bruno, Claudio, and Bruno, Didier
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SKELETAL maturity ,ULTRASONIC imaging ,GROWTH disorders ,METACARPOPHALANGEAL joint ,IONIZING radiation - Abstract
Background: Radiographic bone age determination is part of the routine evaluation of suspected growth disorders. Simplicity and low cost are its major advantages, but although the effective dose of ionizing radiation is low, it should be taken into consideration given its cumulative effect. Objectives: To assess the chronological ultrasonographic emergence of the ossification centers of the hand and wrist. Materials and methods: Cross-sectional study of healthy patients ages 1 to 24 months ( n = 498) from Buenos Aires, Argentina. All patients underwent ultrasonographic evaluation of the left hand and wrist to identify the different bone nuclei; a subgroup of infants had their nuclei measured ( n = 228). Results: Girls showed an earlier emergence of the evaluated nuclei and a trend to a greater size than age-matched boys. Size-for-age relation showed linear increase. Carpal bones (capitate and hamate) were the first to appear, as early as from the first 3 months of life, an age gap not thoroughly present on the radiographic atlas developed by Greulich and Pyle. The distal epiphysis of the radius and the second metacarpophalangeal joint (index finger) followed in order of emergence. The proximal epiphysis of the first metacarpal bone (thumb) was the last to emerge and was infrequently found on boys at age 24 months. Overall, these findings are in accordance with the radiographic atlas. An ultrasonography atlas of the left hand and wrist was outlined for girls and boys. Conclusion: Conventional ultrasonography allows proper identification of the ossification centers of the hand and wrist and may become an innocuous follow-up tool for patients with growth disorders. [ABSTRACT FROM AUTHOR]
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- 2015
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16. Centronuclear myopathies: genotype-phenotype correlation and frequency of defined genetic forms in an Italian cohort.
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Fattori, Fabiana, Maggi, Lorenzo, Bruno, Claudio, Cassandrini, Denise, Codemo, Valentina, Catteruccia, Michela, Tasca, Giorgio, Berardinelli, Angela, Magri, Francesca, Pane, Marika, Rubegni, Anna, Santoro, Lucio, Ruggiero, Lucia, Fiorini, Patrizio, Pini, Antonella, Mongini, Tiziana, Messina, Sonia, Brisca, Giacomo, Colombo, Irene, and Astrea, Guja
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MUSCLE diseases ,PHENOTYPES ,GENETICS ,GENETIC pleiotropy ,GENOTYPES - Abstract
Centronuclear myopathies (CNMs) are a group of clinically and genetically heterogeneous muscle disorders. To date, mutation in 7 different genes has been reported to cause CNMs but 30 % of cases still remain genetically undefined. Genetic investigations are often expensive and time consuming. Clinical and morphological clues are needed to facilitate genetic tests and to choose the best approach for genetic screening. We aimed to describe genotype-phenotype correlation in an Italian cohort of patients affected by CNMs, to define the relative frequencies of its defined genetic forms and to draw a diagnostic algorithm to address genetic investigations. We recruited patients with CNMs from all the Italian tertiary neuromuscular centers following clinical and histological criteria. All selected patients were screened for the four 'canonical' genes related to CNMs: MTM1, DNM2, RYR1 and BIN1. Pathogenetic mutations were found in 38 of the 54 screened patients (70 %), mostly in patients with congenital onset (25 of 30 patients, 83 %): 15 in MTM1, 6 in DNM2, 3 in RYR1 and one in TTN. Among the 13 patients with a childhood-adolescence onset, mutations were found in 6 patients (46 %), all in DNM2. In the group of the 11 patients with adult onset, mutations were identified in 7 patients (63 %), again in DNM2, confirming that variants in this gene are relatively more common in late-onset phenotypes. The present study provides the relative molecular frequency of centronuclear myopathy and of its genetically defined forms in Italy and also proposes a diagnostic algorithm to be used in clinical practice to address genetic investigations. [ABSTRACT FROM AUTHOR]
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- 2015
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17. Redefining phenotypes associated with mitochondrial DNA single deletion.
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Mancuso, Michelangelo, Orsucci, Daniele, Angelini, Corrado, Bertini, Enrico, Carelli, Valerio, Comi, Giacomo, Donati, Maria, Federico, Antonio, Minetti, Carlo, Moggio, Maurizio, Mongini, Tiziana, Santorelli, Filippo, Servidei, Serenella, Tonin, Paola, Toscano, Antonio, Bruno, Claudio, Bello, Luca, Caldarazzo Ienco, Elena, Cardaioli, Elena, and Catteruccia, Michela
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KEARNS-Sayre syndrome ,GENETICS of eye diseases ,PEARSON marrow-pancreas syndrome ,LIPID metabolism disorders ,MITOCHONDRIAL DNA ,GENETICS - Abstract
Progressive external ophthalmoplegia (PEO), Kearns-Sayre syndrome (KSS) and Pearson syndrome are the three sporadic clinical syndromes classically associated with single large-scale deletions of mitochondrial DNA (mtDNA). PEO plus is a term frequently utilized in the clinical setting to identify patients with PEO and some degree of multisystem involvement, but a precise definition is not available. The purpose of the present study is to better define the clinical phenotypes associated with a single mtDNA deletion, by a retrospective study on a large cohort of 228 patients from the database of the 'Nation-wide Italian Collaborative Network of Mitochondrial Diseases'. In our database, single deletions account for about a third of all patients with mtDNA-related disease, more than previously recognized. We elaborated new criteria for the definition of PEO and 'KSS spectrum' (a category of which classic KSS represents the most severe extreme). The criteria for 'KSS spectrum' include the resulting multisystem clinical features associated with the KSS features, and which therefore can predict their presence or subsequent development. With the new criteria, we were able to classify nearly all our single-deletion patients: 64.5 % PEO, 31.6 % KSS spectrum (including classic KSS 6.6 %) and 2.6 % Pearson syndrome. The deletion length was greater in KSS spectrum than in PEO, whereas heteroplasmy was inversely related with age at onset. We believe that the new phenotype definitions implemented here may contribute to a more homogeneous patient categorization, which will be useful in future cohort studies of natural history and clinical trials. [ABSTRACT FROM AUTHOR]
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- 2015
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18. The Trapped Vortex Combustor: An Advanced Combustion Technology for Aerospace and Gas Turbine Applications.
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Syred, Nick, Khalatov, Artem, Bruno, Claudio, and Losurdo, M.
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In the past, it has been demonstrated that combustion technology based on premixing reactants with combustion products may improve both combustion efficiency and emissions for some industrial applications. Work currently in progress in the European Union aims at developing applications to use this combustion strategy for gas turbines and aerospace applications. The challenge is to provide a new class of combustors performing at a high combustion efficiency and low emission indices, together with multifuel capability (gas and liquid fuels), and low pressure drop. The trapped vortex combustor (TVC) may be considered a very promising form of technology for both pollutant emissions and pressure drop reduction. This strategy is based on mixing hot combustion products and reactants at a high rate. Turbulence occurring in a TVC combustion chamber is "trapped" within a cavity where reactants are injected and efficiently mixed. Since part of the combustion occurs within the recirculation zone, a "typically" flameless regime can be achieved, while a trapped turbulent vortex may provide significant pressure drop reduction. The work presented in this paper is the result of having investigated all of these aspects. [ABSTRACT FROM AUTHOR]
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- 2007
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19. View to the future and exploration of our Galaxy.
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Czysz, Paul A. and Bruno, Claudio
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- 2006
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20. Stellar and quasi-stellar propulsion.
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Czysz, Paul A. and Bruno, Claudio
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- 2006
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21. Exploration of our Solar System.
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Czysz, Paul A. and Bruno, Claudio
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- 2006
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22. Earth-Moon system: establishing a Solar System presence.
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Czysz, Paul A. and Bruno, Claudio
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- 2006
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23. Introduction.
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Czysz, Paul A. and Bruno, Claudio
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- 2006
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24. Commercial near Earth launcher: propulsion.
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Czysz, Paul A. and Bruno, Claudio
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- 2006
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25. Commercial near Earth space launcher: a perspective.
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Czysz, Paul A. and Bruno, Claudio
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- 2006
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26. Overview.
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Czysz, Paul A. and Bruno, Claudio
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- 2006
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27. Earth orbit on-orbit operations in near Earth orbit, a necessary second step.
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Czysz, Paul A. and Bruno, Claudio
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- 2006
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28. Our progress appears to be impeded.
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Czysz, Paul A. and Bruno, Claudio
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- 2006
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29. The m.3243A>G mitochondrial DNA mutation and related phenotypes. A matter of gender?
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Mancuso, Michelangelo, Orsucci, Daniele, Angelini, Corrado, Bertini, Enrico, Carelli, Valerio, Comi, Giacomo, Donati, Alice, Minetti, Carlo, Moggio, Maurizio, Mongini, Tiziana, Servidei, Serenella, Tonin, Paola, Toscano, Antonio, Uziel, Graziella, Bruno, Claudio, Ienco, Elena, Filosto, Massimiliano, Lamperti, Costanza, Catteruccia, Michela, and Moroni, Isabella
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MITOCHONDRIAL encephalomyopathies ,LACTIC acidosis ,STROKE ,MITOCHONDRIAL DNA ,PHENOTYPES - Abstract
The m.3243A>G 'MELAS' (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) mutation is one of the most common point mutations of the mitochondrial DNA, but its phenotypic variability is incompletely understood. The aim of this study was to revise the phenotypic spectrum associated with the mitochondrial m.3243A>G mutation in 126 Italian carriers of the mutation, by a retrospective, database-based study ('Nation-wide Italian Collaborative Network of Mitochondrial Diseases'). Our results confirmed the high clinical heterogeneity of the m.3243A>G mutation. Hearing loss and diabetes were the most frequent clinical features, followed by stroke-like episodes. 'MIDD' (maternally-inherited diabetes and deafness) and 'PEO' (progressive external ophthalmoplegia) are nosographic terms without any real prognostic value, because these patients may be even more prone to the development of multisystem complications such as stroke-like episodes and heart involvement. The 'MELAS' acronym is convincing and useful to denote patients with histological, biochemical and/or molecular evidence of mitochondrial disease who experience stroke-like episodes. Of note, we observed for the first time that male gender could represent a risk factor for the development of stroke-like episodes in Italian m.3243A>G carriers. Gender effect is not a new concept in mitochondrial medicine, but it has never been observed in MELAS. A better elucidation of the complex network linking mitochondrial dysfunction, apoptosis, estrogen effects and stroke-like episodes may hold therapeutic promises. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
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30. Neuromuscular Disorders in Zebrafish: State of the Art and Future Perspectives.
- Author
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Pappalardo, Andrea, Pitto, Letizia, Fiorillo, Chiara, Alice Donati, M., Bruno, Claudio, and Santorelli, Filippo
- Abstract
Neuromuscular disorders are a broad group of inherited conditions affecting the structure and function of the motor system with polymorphic clinical presentation and disease severity. Although individually rare, collectively neuromuscular diseases have an incidence of 1 in 3,000 and represent a significant cause of disability of the motor system. The past decade has witnessed the identification of a large number of human genes causing muscular disorders, yet the underlying pathogenetic mechanisms remain largely unclear, limiting the developing of targeted therapeutic strategies. To overcome this barrier, model systems that replicate the different steps of human disorders are increasingly being developed. Among these, the zebrafish ( Danio rerio) has emerged as an excellent organism for studying genetic disorders of the central and peripheral motor systems. In this review, we will encounter most of the available zebrafish models for childhood neuromuscular disorders, providing a brief overview of results and the techniques, mainly transgenesis and chemical biology, used for genetic manipulation. The amount of data collected in the past few years will lead zebrafish to became a common functional tool for assessing rapidly drug efficacy and off-target effects in neuromuscular diseases and, furthermore, to shed light on new etiologies emerging from large-scale massive sequencing studies. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
31. Neuromuscular Disorders of Glycogen Metabolism.
- Author
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Gazzerro, Elisabetta, Andreu, Antoni, and Bruno, Claudio
- Abstract
Disorders of glycogen metabolism are inborn errors of energy homeostasis affecting primarily skeletal muscle, heart, liver, and, less frequently, the central nervous system. These rare diseases are quite variable in age of onset, symptoms, morbidity, and mortality. This review provides an update on disorders of glycogen metabolism affecting skeletal muscle exclusively or predominantly. From a pathogenetic perspective, we classify these diseases as primary, if the defective enzyme is directly involved in glycogen/glucose metabolism, or secondary, if the genetic mutation affects proteins which indirectly regulate glycogen or glucose processing. In addition to summarizing the most recent clinical reports in this field, we briefly describe animal models of human glycogen disorders. These experimental models are greatly improving the understanding of the pathogenetic mechanisms underlying the muscle degenerative process associated to these diseases and provide in vivo platforms to test new therapeutic strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
32. TRPV4 mutations in children with congenital distal spinal muscular atrophy.
- Author
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Fiorillo, Chiara, Moro, Francesca, Brisca, Giacomo, Astrea, Guja, Nesti, Claudia, Bálint, Zoltán, Olschewski, Andrea, Meschini, Maria, Guelly, Christian, Auer-Grumbach, Michaela, Battini, Roberta, Pedemonte, Marina, Romano, Alessandro, Menchise, Valeria, Biancheri, Roberta, Santorelli, Filippo, and Bruno, Claudio
- Abstract
Inherited disorders characterized by motor neuron loss and muscle weakness are genetically heterogeneous. The recent identification of mutations in the gene encoding transient receptor potential vanilloid 4 ( TRPV4) in distal spinal muscular atrophy (dSMA) prompted us to screen for TRPV4 mutations in a small group of children with compatible phenotype. In a girl with dSMA and vocal cord paralysis, we detected a new variant (p.P97R) localized in the cytosolic N-terminus of the TRPV4 protein, upstream of the ankyrin-repeat domain, where the great majority of disease-associated mutations reside. In another child with congenital dSMA, in this case associated with bone abnormalities, we detected a previously reported mutation (p.R232C). Functional analysis of the novel p.P97R mutation in a heterologous system demonstrated a loss-of-function mechanism. Protein localization studies in muscle, skin, and cultured skin fibroblasts from both patients showed normal protein expression. No TRPV4 mutations were detected in four children with dSMA without bone or vocal cord involvement. Adding to the clinical and molecular heterogeneity of TRPV4-associated diseases, our results suggest that molecular testing of the TRPV4 gene is warranted in cases of congenital dSMA with bone abnormalities and vocal cord paralysis. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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33. The spectrum of GNE mutations: allelic heterogeneity for a common phenotype.
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Grandis, Marina, Gulli, Rossella, Cassandrini, Denise, Gazzerro, Elisabetta, Benedetti, Luana, Narciso, Eleonora, Nobbio, Lucilla, Bruno, Claudio, Minetti, Carlo, Bellone, Emilia, Reni, Lizia, Mancardi, Giovanni Luigi, Mandich, Paola, and Schenone, Angelo
- Subjects
MUSCLE diseases ,PHENOTYPES ,HISTOPATHOLOGY ,HETEROGENEITY ,PREGNANT women - Abstract
Hereditary inclusion body myopathy (IBM2) was mainly reported in Middle Eastern Jewish patients. Distal myopathy with rimmed vacuoles has been described as a worldwide distributed distal myopathy. Both diseases are caused by mutations of the UDP- N-acetylglucosamine 2-epimerase/ N-acetylmannosamine kinase ( GNE) gene. Herein we report two patients: an Egyptian Muslim patient with the “common” Middle Eastern mutation (M712T), rarely described in non-Jewish patients; and an Italian patient carrying a novel GNE mutation (L179F) in the epimerase domain. Our patients share common clinical and histopathological features, with some interesting aspects. The first patient presented a clinical deterioration during her first pregnancy confirming that an increased requirement of sialic acid during pregnancy may trigger a clinical worsening. The second patient showed a slowly progressive deterioration, different from other patients carrying mutations in the epimerase domain, who had a severe and rapid progression. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
34. Caveolinopathies: from the biology of caveolin-3 to human diseases.
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Gazzerro, Elisabetta, Sotgia, Federica, Bruno, Claudio, Lisanti, Michael P., and Minetti, Carlo
- Subjects
CARDIOMYOPATHIES ,MUSCULAR dystrophy ,CELL membranes ,CYTOPLASM ,PROTEINS ,MUSCLE cells - Abstract
In muscle tissue the protein caveolin-3 forms caveolae – flask-shaped invaginations localized on the cytoplasmic surface of the sarcolemmal membrane. Caveolae have a key role in the maintenance of plasma membrane integrity and in the processes of vesicular trafficking and signal transduction. Mutations in the caveolin-3 gene lead to skeletal muscle pathology through multiple pathogenetic mechanisms. Indeed, caveolin-3 deficiency is associated to sarcolemmal membrane alterations, disorganization of skeletal muscle T-tubule network and disruption of distinct cell-signaling pathways. To date, there have been 30 caveolin-3 mutations identified in the human population. Caveolin-3 defects lead to four distinct skeletal muscle disease phenotypes: limb girdle muscular dystrophy, rippling muscle disease, distal myopathy, and hyperCKemia. In addition, one caveolin-3 mutant has been described in a case of hypertrophic cardiomyopathy. Many patients show an overlap of these symptoms and the same mutation can be linked to different clinical phenotypes. This variability can be related to additional genetic or environmental factors. This review will address caveolin-3 biological functions in muscle cells and will describe the muscle and heart disease phenotypes associated with caveolin-3 mutations. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
35. SMN transcript levels in leukocytes of SMA patients determined by absolute real-time PCR.
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Tiziano, Francesco Danilo, Pinto, Anna Maria, Fiori, Stefania, Lomastro, Rosa, Messina, Sonia, Bruno, Claudio, Pini, Antonella, Pane, Marika, D'Amico, Adele, Ghezzo, Alessandro, Bertini, Enrico, Mercuri, Eugenio, Neri, Giovanni, and Brahe, Christina
- Subjects
SPINAL muscular atrophy ,MUSCULAR atrophy ,SPINAL cord diseases ,NEUROMUSCULAR diseases ,BIOMARKERS - Abstract
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by homozygous mutations of the SMN1 gene. Three forms of SMA are recognized (type I–III) on the basis of clinical severity. All patients have at least one or more (usually 2–4) copies of a highly homologous gene (SMN2), which produces insufficient levels of functional SMN protein, because of alternative splicing of exon 7. Recently, evidence has been provided that SMN2 expression can be enhanced by pharmacological treatment. However, no reliable biomarkers are available to test the molecular efficacy of the treatments. At present, the only potential biomarker is the dosage of SMN products in peripheral blood. However, the demonstration that SMN full-length (SMN-fl) transcript levels are reduced in leukocytes of patients compared with controls remains elusive (except for type I). We have developed a novel assay based on absolute real-time PCR, which allows the quantification of SMN1-fl/SMN2-fl transcripts. For the first time, we have shown that SMN-fl levels are reduced in leukocytes of type II–III patients compared with controls. We also found that transcript levels are related to clinical severity as in type III patients SMN2-fl levels are significantly higher compared with type II and directly correlated with functional ability in type II patients and with age of onset in type III patients. Moreover, in haploidentical siblings with discordant phenotype, the less severely affected individuals showed significantly higher transcript levels. Our study shows that SMN2-fl dosage in leukocytes can be considered a reliable biomarker and can provide the rationale for SMN dosage in clinical trials. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
36. Novel mutations in CLN8 in Italian variant late infantile neuronal ceroid lipofuscinosis: another genetic hit in the Mediterranean.
- Author
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Cannelli, Natalia, Cassandrini, Denise, Bertini, Enrico, Striano, Pasquale, Fusco, Lucia, Gaggero, Roberto, Specchio, Nicola, Biancheri, Roberta, Vigevano, Federico, Bruno, Claudio, Simonati, Alessandro, Zara, Federico, and Santorelli, Filippo M.
- Subjects
NEURONAL ceroid-lipofuscinosis ,HUMAN molecular genetics ,NEURODEGENERATION ,DEMYELINATION ,NEUROGENETICS - Abstract
Neuronal ceroid lipofuscinoses (NCLs) are autosomal recessive neurodegenerative disorders typically characterized by the accumulation of autofluorescent material in tissues. On the basis of clinical features, age at onset, and molecular genetic defects, it is possible to distinguish at least nine forms. The CLN8 form was first described in Finland, where all the patients are homozygous for a p.Arg24Gly mutation in CLN8. More recently, it has been found that a subset of a Turkish variant of late infantile NCL (v-LINCL) is also associated with CLN8 mutations. To identify the molecular defect in Italian patients with v-LINCL, the CLN8 gene was directly sequenced in 10 patients. Controls were screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Five fluorescent-labeled microsatellite markers covering 1 cM around the gene were used for haplotype analysis. In three Italian v-LINCL patients, identified in a small area in southern Italy, we detected four new mutations in CLN8: c.66delG (p.Gly22fs), c.88G>C (p.Ala30Pro), c.473A>G (p.Tyr158Cys), and c.581A>G (p.Gln194Arg). The single-base deletion was found in two unrelated patients. The novel missense mutations were not identified in ethnically matched control chromosomes. Our findings expand the number of CLN8 variants and corroborate the notion that CLN8 patients are not confined to the Finnish population. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
37. Congenital myopathies.
- Author
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Bruno, Claudio and Minetti, Carlo
- Abstract
The congenital myopathies encompass a group of neuromuscular disorders with characteristic morphologic abnormalities in skeletal muscle, including nemaline myopathy, central core disease, multi-minicore disease, and myotubular myopathy. Giant steps have been made in our understanding of the molecular bases of these disorders, all of which show remarkable genetic heterogeneity. This review of congenital myopathies examines progress in defining clinical diagnostic criteria and novel genetic advances that have provided important clues regarding their pathogeneses. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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- View/download PDF
38. Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy.
- Author
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Minetti, Carlo, Sotgia, Federica, Bruno, Claudio, Scartezzini, Paolo, Broda, Paolo, Bado, Massimo, Masetti, Emiliana, Mazzocco, Michela, Egeo, Aliana, Donati, Maria Alice, Volonté, Daniela, Galbiati, Ferruccio, Cordone, Giuseppe, Bricarelli, Franca Dagna, Lisanti, Michael P., and Zara, Federico
- Published
- 1998
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- View/download PDF
39. Deficiency of hyccin, a newly identified membrane protein, causes hypomyelination and congenital cataract.
- Author
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Zara, Federico, Biancheri, Roberta, Bruno, Claudio, Bordo, Laura, Assereto, Stefania, Gazzerro, Elisabetta, Sotgia, Federica, Wang, Xiao Bo, Gianotti, Stefania, Stringara, Silvia, Pedemonte, Marina, Uziel, Graziella, Rossi, Andrea, Schenone, Angelo, Tortori-Donati, Paolo, van der Knaap, Marjo S., Lisanti, Michael P., and Minetti, Carlo
- Subjects
MOLECULAR pathology ,DEMYELINATION ,MEMBRANE proteins ,HUMAN molecular genetics ,CATARACT ,GENETICS - Abstract
We describe a new autosomal recessive white matter disorder ('hypomyelination and congenital cataract') characterized by hypomyelination of the central and peripheral nervous system, progressive neurological impairment and congenital cataract. We identified mutations in five affected families, resulting in a deficiency of hyccin, a newly identified 521–amino acid membrane protein. Our study highlights the essential role of hyccin in central and peripheral myelination. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
40. Erratum to: Muscle MRI in neutral lipid storage disease (NLSD).
- Author
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Garibaldi, Matteo, Tasca, Giorgio, Diaz-Manera, Jordi, Ottaviani, Pierfancesco, Laschena, Francesco, Pantoli, Donatella, Gerevini, Simonetta, Fiorillo, Chiara, Maggi, Lorenzo, Tasca, Elisabetta, D'amico, Adele, Musumeci, Olimpia, Toscano, Antonio, Bruno, Claudio, Massa, Roberto, Angelini, Corrado, Bertini, Enrico, Antonini, Giovanni, and Pennisi, Elena
- Subjects
LIPIDOSES ,MAGNETIC resonance imaging - Abstract
A correction to the article "Muscle MRI in Neutral Lipid Storage Disease (NLSD)" that was published in the July 2017 issue is presented.
- Published
- 2017
- Full Text
- View/download PDF
41. Erratum to: Redefining phenotypes associated with mitochondrial DNA single deletion.
- Author
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Mancuso, Michelangelo, Orsucci, Daniele, Angelini, Corrado, Bertini, Enrico, Carelli, Valerio, Comi, Giacomo, Donati, Maria, Federico, Antonio, Minetti, Carlo, Moggio, Maurizio, Mongini, Tiziana, Santorelli, Filippo, Servidei, Serenella, Tonin, Paola, Toscano, Antonio, Bruno, Claudio, Bello, Luca, Ienco, Elena, Cardaioli, Elena, and Catteruccia, Michela
- Subjects
MITOCHONDRIAL DNA ,PHENOTYPES ,GENETIC research - Abstract
A correction to the article "Redefining Phenotypes Associated With Mitochondrial DNA Single Deletion" in a 2015 issue of the "Journal of Neurology" is presented.
- Published
- 2015
- Full Text
- View/download PDF
42. Caveolinopathies: from the biology of caveolin-3 to human diseases.
- Author
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Gazzerro, Elisabetta, Sotgia, Federica, Bruno, Claudio, Lisanti, Michael P., and Minetti, Carlo
- Subjects
DISEASES - Abstract
A correction to the article "Caveolinopathies: from the biology of caveolin-3 to human diseases," published in the July 8, 2009 issue is presented.
- Published
- 2009
- Full Text
- View/download PDF
43. Spinal muscular atrophy: state of the art and new therapeutic strategies.
- Author
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Messina, Sonia, Sframeli, Maria, Maggi, Lorenzo, D’Amico, Adele, Bruno, Claudio, Comi, Giacomo, Mercuri, Eugenio, and D'Amico, Adele
- Abstract
Spinal muscular atrophy (SMA) is a severe disorder of motor neurons and the most frequent cause of genetic mortality, due to respiratory complications. We are facing an exciting era with three available therapeutic options in a disease considered incurable for more than a century. However, the availability of effective approaches has raised up ethical, medical, and financial issues that are routinely faced by the SMA community. Each therapeutic strategy has its weaknesses and strengths and clinicians need to know them to optimize clinical care. In this review, the state of the art and the results and challenges of the new SMA therapeutic strategies are highlighted. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
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