(Epi)genetic profiling of extraembryonic and postnatal tissues from female monozygotic twins discordant for Beckwith–Wiedemann syndrome

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Influência do tratamento intensivo com suporte de peso corporal na função motora de crianças com paralisia cerebral

A aquisição da marcha sob o aspecto neuromotor da reabilitação vem a ser o principal desígnio do terapeuta durante a elaboração do plano de tratamento do paciente com paralisia cerebral, uma vez que a marcha representa não só um ganho da habilidade de locomover-se, mas também um conjunto de reações e padrões de movimento que auxiliam na função motora. Objetivo: Analisar os efeitos de um tratamento intensivo por meio do suporte de peso corporal em crianças com paralisia cerebral. Métodos: Participaram do estudo 10 crianças com paralisia cerebral, GMFCS nível IV ou V, idade entre 4 a 9 anos. Onde foram realizadas sessões diárias com suporte de peso corporal em esteira ergométrica com auxílio de terapeutas para executar o padrão de marcha mais próximo da normalidade, com pontos chaves em joelho e tornozelo com duração de 30 minutos de tratamento e intervalo de 24 horas, por um período de 10 dias. Para fins de avaliação pré e pós-intervenção, utilizando a escala de medição da função motora grossa GMFM, e da flexibilidade pelo Flexiteste. Resultados: Foi possível constatar um aumento relevante na função motora grossa dos sujeitos, onde o domínio Deitar e Rolar obteve maior pontuação, com um aumento de 10,77%. Sentar demonstrou aumento de 3,80%, Engatinhar e Ajoelhar 6,43% e o domínio Em Pé 3,45%. Relativo ao Flexiteste, a média entre os sujeitos relatou aumento expressivo de 4,2 pontos. Já em análise individual, percebe-se que 3 indivíduos obtiveram aumento de score de 6 pontos. Conclusão: Um protocolo intensivo de curta duração é capaz de trazer ganhos de flexibilidade e motores rápidos a crianças que possuem quadro de paralisia cerebral.The acquisition of gait under the neuromotor aspect of rehabilitation is the main goal of the therapist during the elaboration of the treatment plan of the patient with cerebral palsy, since gait represents not only a gain in the ability to move, but also a set of reactions and movement patterns that aid in motor function. Objective: To analyze the effects of intensive treatment by means of body weight support in children with cerebral palsy. Method: Ten children with cerebral palsy, GMFCS level IV or V, age between 4 and 9 years participated in the study. Where daily sessions were performed with body weight support on a treadmill with the help of therapists to perform the walking pattern closest to normal, with key points in the knee and ankle lasting 30 minutes of treatment and 24 hour intervals for one period of 10 days. For purposes of pre and post-intervention evaluation, using the GMFM gross motor function measurement scale, and Flexitest flexibility. Results: It was possible to observe a significant increase in the gross motor function of the subjects, where the lie down and roll domain obtained a higher score, with an increase of 10.77%. To sit demonstrated a 3.80% increase, Crawling and Kneeling 6.43% and the Standing Foot 3.45%. Relative to Flexitest, the mean between subjects reported a significant increase of 4.2 points. In the individual analysis, it was observed that 3 subjects had a 6-point score increase. Conclusions: An intensive short-duration protocol is capable of bringing flexibility gains and fast motor to children with cerebral palsy

Administration of Harmine and Imipramine Alters Creatine Kinase and Mitochondrial Respiratory Chain Activities in the Rat Brain

The present study evaluated mitochondrial respiratory chain and creatine kinase activities after administration of harmine (5, 10, and 15 mg/kg) and imipramine (10, 20, and 30 mg/kg) in rat brain. After acute treatment occurred an increase of creatine kinase in the prefrontal with imipramine (20 and 30 mg/kg) and harmine in all doses, in the striatum with imipramine (20 and 30 mg/kg) and harmine (5 and 10 mg/kg); harmine (15 mg/kg) decreased creatine kinase. In the chronic treatment occurred an increase of creatine kinase with imipramine (20 mg/kg), harmine (5 mg/kg) in the prefrontal with imipramine (20 and 30 mg/kg) and harmine (5 and 10 mg/kg) in the striatum. In the acute treatment, the complex I increased in the prefrontal with harmine (15 mg/kg) and in the striatum with harmine (10 mg/kg); the complex II decreased with imipramine (20 and 30 mg/kg) in the striatum; the complex IV increased with imipramine (30 mg/kg) in the striatum. In the chronic treatment, the complex I increased with harmine (5 mg/kg) in the prefrontal; the complex II increased with imipramine (20 mg/kg) in the prefrontal; the complex IV increased with harmine (5 mg/kg) in the striatum. Finally, these findings further support the hypothesis that harmine and imipramine could be involved in mitochondrial function

Case report: a typical Silver-Russell syndrome patient with hand dystonia: the valuable support of the consensus statement to the wide syndromic spectrum

The amount of Insulin Growth Factor 2 (IGF2) controls the rate of embryonal and postnatal growth. The IGF2 and adjacent H19 are the imprinted genes of the telomeric cluster in the 11p15 chromosomal region regulated by differentially methylated regions (DMRs) or imprinting centers (ICs): H19/IGF2:IG-DMR (IC1). Dysregulation due to IC1 Loss-of-Methylation (LoM) or Gain-of-Methyaltion (GoM) causes Silver–Russell syndrome (SRS) or Beckwith–Wiedemann syndrome (BWS) disorders associated with growth retardation or overgrowth, respectively. Specific features define each of the two syndromes, but isolated asymmetry is a common cardinal feature, which is considered sufficient for a diagnosis in the BWS spectrum. Here, we report the case of a girl with right body asymmetry, which suggested BWS spectrum. Later, BWS/SRS molecular analysis identified IC1_LoM revealing the discrepant diagnosis of SRS. A clinical re-evaluation identified a relative macrocephaly and previously unidentified growth rate at lower limits of normal at birth, feeding difficulties, and asymmetry. Interestingly, and never previously described in IC1_LoM SRS patients, since the age of 16, she has developed hand-writer’s cramps, depression, and bipolar disorder. Trio-WES identified a VPS16 heterozygous variant [NM_022575.4:c.2185C>G:p.Leu729Val] inherited from her healthy mother. VPS16 is involved in the endolysosomal system, and its dysregulation is linked to autosomal dominant dystonia with incomplete penetrance and variable expressivity. IGF2 involvement in the lysosomal pathway led us to speculate that the neurological phenotype of the proband might be triggered by the concurrent IGF2 deficit and VPS16 alteration

Long-read sequencing reveals chromothripsis in a molecularly unsolved case of Cornelia de Lange syndrome

Thanks to a long-read sequencing (LRS) approach, in this study, we have reported a molecularly solved case of a proband with a clinical diagnosis of Cornelia de Lange syndrome (CDLS), which is a multisystemic disorder whose causative molecular defects involve cohesin complex genes, with NIPBL located at 5p13.2 accounting for approximately 50%–60% of CDLS cases. The first-tier tests revealed an abnormal karyotype 46,XY,t(5;15)(p13;q25)dn and a preserved NIPBL sequencing. Copy number variants (CNVs) at the translocation breakpoints, in disease genes, or in probably pathogenic loci were excluded by a-CGH analysis. Through fluorescence in situ hybridization (FISH) analysis on derivative chromosome 5, the breakpoint was relocated 3 Mb far from NIPBL 5′UTR, which seemed fully maintained as FISH-probe mapping to the gene showed no split signals. Moreover, tri-color FISH revealed an apparently balanced paracentric inversion including NIPBL on derivative 5. Based on the strong clinical suspicion, we evaluated the NIPBL transcript by RT-qPCR that revealed a normal amount of transcript till exon 22 and a halved amount of the transcript from exon 23 to 3′UTR, indicating the expression of a truncated transcript probably leading to a defective protein. Despite RT-qPCR confirmed the patient’s CDLS clinical diagnosis, the molecular mechanism underlying this event remained to be an unsolved challenge for years. The LRS approach with nanopore technologies was able to fill the gap in this complex scenario and highlighted a chromothripsis event marked out at 5p13.2 by 36 breaks clustered in a 7.3-Mb region. The NIPBL gene was disrupted by 16 breaks and the resulting fragments were relocated in different positions and orientations. LRS confirmed the previous findings, and it has been proven to be crucial to define the complex chromosomal rearrangement in this patient which escaped current diagnostic investigations. Its application in the clinical practice will contribute to solve the unsolved

Fetal cell microchimerism: a protective role in autoimmune thyroid diseases

The physiological persistence of fetal cells in the circulation and tissue of a previously pregnant woman is called fetal cell microchimerism (FCM). It has been hypothesized to play a role in systemic autoimmune disease; however, only limited data are available regarding its role in autoimmune thyroid disease (AITD)

DataSheet1_Long-read sequencing reveals chromothripsis in a molecularly unsolved case of Cornelia de Lange syndrome.docx

Thanks to a long-read sequencing (LRS) approach, in this study, we have reported a molecularly solved case of a proband with a clinical diagnosis of Cornelia de Lange syndrome (CDLS), which is a multisystemic disorder whose causative molecular defects involve cohesin complex genes, with NIPBL located at 5p13.2 accounting for approximately 50%–60% of CDLS cases. The first-tier tests revealed an abnormal karyotype 46,XY,t(5;15)(p13;q25)dn and a preserved NIPBL sequencing. Copy number variants (CNVs) at the translocation breakpoints, in disease genes, or in probably pathogenic loci were excluded by a-CGH analysis. Through fluorescence in situ hybridization (FISH) analysis on derivative chromosome 5, the breakpoint was relocated 3 Mb far from NIPBL 5′UTR, which seemed fully maintained as FISH-probe mapping to the gene showed no split signals. Moreover, tri-color FISH revealed an apparently balanced paracentric inversion including NIPBL on derivative 5. Based on the strong clinical suspicion, we evaluated the NIPBL transcript by RT-qPCR that revealed a normal amount of transcript till exon 22 and a halved amount of the transcript from exon 23 to 3′UTR, indicating the expression of a truncated transcript probably leading to a defective protein. Despite RT-qPCR confirmed the patient’s CDLS clinical diagnosis, the molecular mechanism underlying this event remained to be an unsolved challenge for years. The LRS approach with nanopore technologies was able to fill the gap in this complex scenario and highlighted a chromothripsis event marked out at 5p13.2 by 36 breaks clustered in a 7.3-Mb region. The NIPBL gene was disrupted by 16 breaks and the resulting fragments were relocated in different positions and orientations. LRS confirmed the previous findings, and it has been proven to be crucial to define the complex chromosomal rearrangement in this patient which escaped current diagnostic investigations. Its application in the clinical practice will contribute to solve the unsolved.</p