1,720,963 research outputs found
7q31.32 partial duplication: First report of a child with dysmorphism, autistic spectrum disorder, moderate intellectual disability and, epilepsy. Literature review
No full textIntroduction: Duplication of long arm of chromosome 7(q) is uncommon. It may occur as "pure", isolated anomaly or in association with other mutations involving the same or other chromosomes. "Pure" chromosome 7q duplication has recently been classified by segment involved: the interstitial, proximal, or distal segment of the arm. Attempts to correlate genotype with phenotype in each group has yielded questionable results even though intellective disability and minor dysmorphic features of variable types are typically seen.Material and Methods: In a young boy showing minor facial dysmorphism, language delay, autistic spectrum disorder, epileptic seizures, behavioral disturbances and irritability an array-CGH analysis was carried out.Results: Array-CGH analysis found in the proband a de novo variant of partial duplication of 7q31.32 (122.254.792-122.376.908).Discussion: A very few cases of partial 7q duplication have been reported thus far mainly presenting with clinical signs of dysmorphic features, large head, developmental delay, epileptic seizures and skeletal anomalies. To our knowledge, this is the first report of a case of a de novo variant of 7q31.32 duplication, showing dysmorphic anomalies and neurologic impairment including ASD and seizures. In the 7q31.32 region is located the gene CADPS2, which has been associated to autistic spectrum disorder and other neurologic disorders. In the child, a genotype-phenotype correlation may be hypothesized. Further similar reports may be useful to confirm this observation
Impressive efficacy of the ketogenic diet in a KCNQ2 encephalopathy infant: a case report and exhaustive literature review
No full textBackground: KCNQ2 encephalopathy is characterized by neonatal-onset epilepsy and developmental impairment, due to "de novo" KCNQ2 pathogenic variants. According to literature data, sodium channel blocking agents appear to be the best treatment options for the disease. Reports describing the use of ketogenic diet (KD) in the KCNQ2 pediatric population are limited. The non-conservative amino acid substitution p.Ser122Leu in KCNQ2 is associated with a broad spectrum of inheritance modalities, clinical phenotypes and outcomes; no previous reports of the same variant treated with KD are available in literature. Case description: We described a 22-month-old female with seizure onset on day 2 of life. At three months of age, she presented refractory status epilepticus (SE) that did not respond to midazolam and carbamazepine, which was added once a "de novo" p.Ser122Leu KCNQ2 variant was demonstrated. KD was the only treatment that led to cessation of seizures. The baby maintained seizures remission and achieved neurodevelopmental milestones. Conclusions: To define an overt genotype-phenotype correlation for KCNQ2 pathogenic variants is a challenge; we propose the KD as a valuable treatment for refractory seizures and impaired neurodevelopment in infants harboring "de novo" mutations in the KCNQ2 gene
Pathogenic correlation between mosaic variegated aneuploidy 1 (MVA1) and a novel BUB1B variant: a reappraisal of a severe syndrome.
Full text linkBACKGROUND: The BUB 1 mitotic checkpoint serine/threonine kinase B (BUB1B) gene encodes a key protein in the mitotic spindle checkpoint, which acts as a surveillance mechanism, crucial for the maintenance of the correct chromosome number during cell deviation. Mutations of BUB1B gene are linked to mosaic variegated aneuploidy 1 (MVA1) syndrome, a rare autosomal recessive disorder characterized by widespread mosaic aneuploidies, involving different chromosomes and tissues. MVA1 is clinically characterized by intrauterine growth restriction, post-natal growth retardation, and severe neurologic impairment including microcephaly, developmental delay/intellectual disability, epileptic seizures, and generalized hypotonia. Malignancies are also serious sequelae associated with the disorder. We reported on a case of two-year-old Italian girl with MVA1 who shows severe neurologic impairment, microcephaly and epileptic seizures. MATERIALS AND METHODS: Clinical data collection and genetic diagnosis of the patient were assessed. Mutational analysis covers the chromosomal microarray analysis, the gene methylation pattern studied using the methylation-specific multiplex ligation-dependent probe amplification, and the family-based Whole Exome Sequencing (WES). A literature research based on reported cases of MVA and premature chromatid separation was also included. RESULTS: Karyotyping has revealed 12% of mosaics in the patient who carries a novel variant in BUB1B gene (c.2679A > T, p.Arg893Ser) detected by WES. Thirty-one cases of MVA1 including the present report, and four prenatally diagnosed cases with MVA1 were selected and inspected. CONCLUSION: Clinical and genetic findings reported in the girl strongly suggest a new MVA1 genotype-phenotype correlation and lead to a reappraisal of a severe syndrome. Diagnosis and in-depth follow-up provided worthwhile data
A Young Boy with 21q21.1 Microdeletion Showing Speech Delay, Spastic Diplegia, and MRI Abnormalities: Original Case Report
No full textChromosome 21q deletion syndrome is a rare disorder affecting the long arm of chromosome 21 and manifesting with wide phenotypic features depending on the size and position of the deleted region. In the syndrome, three distinct deleted regions have been distinguished: region 1, from the centromere to approximately 31.2 Mb (21q11.2-q22.11); region 2, from 31.2 to 36 Mb (21q22.11-q22.12); and region 3, from 36 to 37.5 Mb to the telomere (21q22.12-q22.3). The clinical features are highly variable manifesting with mild, poorly recognizable signs or with severe symptoms including craniofacial dysmorphism, growth failure, developmental delay, behavioral/affective abnormalities, and systemic malformations. We report here the case of a young boy with speech delay, mild spastic diplegia, and brain anomalies on magnetic resonance imaging (MRI). The genetic analysis displayed a microdeletion of the long arm of chromosome 21 approximately extending up to 1.08 Mb. Clinical presentation of the patient and cases of 21q21 deletion reported by the literature are discussed
PYRIDOXINE-dependent epilepsy (PDE): An observational study of neonatal cases on the role of pyridoxine in patients treated with standard anti-seizure medications
No full textBackground: The main objective of this study was to evaluate the neurological consequences of delayed pyridoxine administration in patients diagnosed with Pyridoxin Dependent Epilepsies (PDE). Materials and Methods: We reviewed 29 articles, comprising 52 genetically diagnosed PDE cases, ensuring data homogeneity. Three additional cases were included from the General Pediatric Operative Unit of San Marco Hospital. Data collection considered factors like age at the first seizure's onset, EEG reports, genetic analyses, and more. Based on the response to first-line antiseizure medications, patients were categorized into four distinct groups. Follow-up evaluations employed various scales to ascertain neurological, cognitive, and psychomotor developments. Results: Our study includes 55 patients (28 males and 27 females), among whom 15 were excluded for the lack of follow-up data. 21 patients were categorized as "Responder with Relapse", 11 as "Resistant", 6 as "Pyridoxine First Approach", and 2 as "Responders". The neurological outcome revealed 37,5 % with no neurological effects, 37,5 % showed complications in two developmental areas, 15 % in one, and 10 % in all areas. The statistical analysis highlighted a positive correlation between the time elapsed from the administration of pyridoxine after the first seizure and worse neurological outcomes. On the other hand, a significant association was found between an extended latency period (that is, the time that elapsed between the onset of the first seizure and its recurrence) and worse neurological outcomes in patients who received an unfavorable score on the neurological evaluation noted in a subsequent follow-up. Conclusions: The study highlights the importance of early recognition and intervention in PDE. Existing medical protocols frequently overlook the timely diagnosis of PDE. Immediate administration of pyridoxine, guided by a swift diagnosis in the presence of typical symptoms, might improve long-term neurological outcomes, and further studies should evaluate the outcome of PDE neonates promptly treated with Pyridoxine
Molecular Dynamic Simulations to Determine Individualized Therapy: Tetrabenazine for the GNAO1 Encephalopathy E246K Variant
No full textIntroduction: GNAO1 encephalopathy is characterized by severe hypotonia, psychomotor retardation, epilepsy, and movement disorders. Genetic variations in GNAO1 have been linked to neurological symptoms including movement disorders like dystonia. The correlation between the E246K mutation in the Gα subunit and aberrant signal transduction of G proteins has been established but no data are reported regarding the efficacy of medical treatment with tetrabenazine. Methods: Molecular modeling studies were performed to elucidate the molecular mechanisms underlying this mutation. We developed drug efficacy models using molecular dynamic simulations that replicated the behavior of wild-type and mutated proteins in the presence or absence of ligands. Results and discussion: We demonstrated that the absence of the mutation leads to normal signal transduction upon receptor activation by the endogenous ligand, but not in the presence of tetrabenazine. In contrast, the presence of the mutation resulted in abnormal signal transduction in the presence of the endogenous ligand, which was corrected by the drug tetrabenazine. Tetrabenazine was identified as a promising therapeutic option for pediatric patients suffering from encephalopathy due to an E246K mutation in the GNAO1 gene validated through molecular dynamics. This is a potential first example of the use of this technique in a rare neurological pediatric disease
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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