scholarly journals Neurobiologia do autismo infantil

2021 ◽  
Vol 10 (1) ◽  
pp. e11910111495
Author(s):  
Cecília Rezende de Almeida Oliveira ◽  
José Carlos Souza
Keyword(s):  
Tsc1 Gene

Objetivo: discutir as características neurobiológicas do Transtorno do Espectro Autista (TEA) em crianças. Metodologia: foi realizada uma revisão narrativa com artigos dos últimos 10 anos (2010-2020), nas bases de dados PsycINFO, Medline, PubMed, SciELO, LILACS e Periódicos CAPES. Utilizaram-se como descritores “Autismo Infantil”, “Transtorno Autista”, “Infância”, “Ciclo Vital”, “Neurodesenvolvimento Infantil”, “Neurobiologia”, “Neurociências”, “Neuroanatomia”, “Neurofisiologia”, “Transtorno do Espectro Autista” e o Booleano “AND”. Todos estes materiais foram lidos na íntegra, categorizados e, posteriormente, analisados criticamente. Resultados e discussão: em indivíduos com TEA, há uma diminuição da conectividade entre o córtex pré-frontal medial e o córtex cingulado posterior; esta diminuição está relacionada a uma função social inferior quando comparada com crianças normais. Alteração semelhante foi encontrada em relação à rede frontoparietal relacionando-se aos comportamentos repetitivos observados no transtorno. Há, também, a hipótese relacionada a uma disfunção cerebelar e, mais especificamente, que a deleção da Proteína 1 do Complexo Esclerose Tuberosa (TSC1) – gene que codifica a proteína hamartina – nas células de Purkinje, reflita nos déficits sociais e comportamentais em indivíduos com TEA. Além disso, é sugerido que o fenótipo do transtorno esteja associado a uma perturbação nos circuitos que conectam o cerebelo ao córtex pré-frontal medial e, também, a uma maior ativação desta última região. Conclusão: ainda não se tem uma conclusão satisfatória e patognomônica da neurobiologia do TEA em crianças; as alterações neurofuncionais mais comuns no TEA estão relacionadas às redes cerebelares e às Células de Purkinje.

New mutation in TSC1-gene in a sporadic case with initially mild phenotype

2012 ◽  
Vol 43 (02) ◽  
Author(s):  
C Thiels ◽  
C Köhler ◽  
K Weigt-Usinger ◽  
C Sutter ◽  
T Lücke
Keyword(s):  
Sporadic Case ◽  
New Mutation ◽  
Mild Phenotype ◽  
Tsc1 Gene

scholarly journals A mutation screen of the TSC1 gene reveals 26 protein truncating mutations and 1 splice site mutation in a panel of 79 tuberous sclerosis patients

1998 ◽  
Vol 62 (3) ◽  
pp. 203-213 ◽  
Author(s):  
J. M. YOUNG ◽  
M. W. BURLEY ◽  
S. J. JEREMIAH ◽  
D. JEGANATHAN ◽  
R. EKONG ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Splice Site ◽  
Splice Site Mutation ◽  
Site Mutation ◽  
Tsc1 Gene ◽  
Mutation Screen

scholarly journals Electroacupuncture Reduces Weight in Diet-Induced Obese Rats via Hypothalamic Tsc1 Promoter Demethylation and Inhibition of the Activity of mTORC1 Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Jincheng Leng ◽  
Feng Xiong ◽  
Junpeng Yao ◽  
Xiahuan Dai ◽  
Yulei Luo ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Body Fat ◽  
Mammalian Target Of Rapamycin ◽  
Gene Promoter ◽  
Chow Group ◽  
Diet Group ◽  
The Body ◽  
Sprague Dawley ◽  
Tsc1 Gene ◽  
Mtorc1 Signaling

Subject. The study aimed to investigate the mechanism of electroacupuncture reducing weight via tuberous sclerosis complex 1 (Tsc1) promoter methylation, inhibiting the mammalian target of rapamycin complex 1 (mTORC1) pathway. Materials and Methods. Male Sprague-Dawley rats were divided into chow-fed group (chow group) or high-fat diet group (HF group) for 14 weeks. The obesity rats in HF group were randomly divided into electroacupuncture group (EA group) and diet-induced obesity (DIO) group, which received EA stimulation on bilateral ST25, RN12, SP6, and ST36 for 4 weeks or no further treatment, respectively. Methylation of the Tsc1 gene promoter and expression of agouti-related protein (AgRP), neuropeptide Y (NPY), and proopiomelanocortin (PoMC) were detected at the 18th week. Results. At week 18, weight, body fat, and the body fat rate in DIO group were significantly higher than those of the chow and EA group. Compared with the chow group, the DIO group had increased methylation of the Tsc1 gene promoter and expression of mTORC1, AgRP, and NPY gene and decreased PoMC in the hypothalamus; after EA, methylation of the Tsc1 gene promoter, mRNA, and protein of the mTORC1 and expression of AgRP and NPY gene decreased and PoMC increased significantly. Conclusions. Our study could shed light on the potential pathway where EA exerts effects on the mechanism of EA treatment for obesity through the hypothalamic Tsc1 promoter demethylation and inhibition of the activity of mTORC1 signaling pathway.

scholarly journals Early diagnosis of a newborn with tuberous sclerosis caused by a genetic mutation

2021 ◽  
Vol 49 (8) ◽  
pp. 030006052110358
Author(s):  
Lin Qiao ◽  
Yuting Yang ◽  
Dongmei Yue
Keyword(s):  
Genetic Testing ◽  
Early Diagnosis ◽  
Tuberous Sclerosis ◽  
De Novo ◽  
Clinical Manifestations ◽  
De Novo Mutation ◽  
Heterozygous Mutation ◽  
Loss Of Function ◽  
Autosomal Dominant Disorder ◽  
Tsc1 Gene

Objective Tuberous sclerosis (TSC) is an autosomal dominant disorder, often detected during childhood. We present the results of genetic testing in a newborn with suspected TSC. Methods A newborn with no specific clinical manifestations of TSC showed evidence of TSC on magnetic resonance imaging and echocardiography. Next-generation sequencing (NGS) and multiple ligation-dependent probe amplification (MLPA) of the TSC1 and TSC2 gene exons were carried out to confirm the diagnosis. Results The results of MLPA were negative, but NGS showed a heterozygous mutation in the TSC1 gene comprising insertion of a T residue at c.2165 (exon 17) to c.2166 (exon 17), indicating a loss of function mutation. These results were verified by Sanger sequencing. This genetic change was present in the newborn but the parental genotypes were wild-type, indicating a de novo mutation. Conclusions In this case, a case of TSC caused by a heterozygous mutation in the TSC1 gene was confirmed by NGS sequencing. This indicates the suitability of genetic testing for the early diagnosis of clinically rare and difficult-to-diagnose diseases, to guide clinical treatment.

scholarly journals Mesenchymal Stem Cell-Specific and Preosteoblast-Specific Ablation of TSC1 in Mice Lead to Severe and Slight Spinal Dysplasia, Respectively

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Cheng Yang ◽  
Jianwen Liao ◽  
Pinglin Lai ◽  
Hai Huang ◽  
Shicai Fan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Body Size ◽  
Mesenchymal Stem Cell ◽  
Endochondral Ossification ◽  
Intervertebral Discs ◽  
Tsc1 Gene ◽  
Spine Development ◽  
Old Mice ◽  
Deficient Mice ◽  
Specific Deletion

Background. TSC1-related signaling plays a pivotal role in intramembranous and endochondral ossification processes during skeletogenesis. This study was aimed at determining the significance of the TSC1 gene at different stages of spinal development. Materials and Methods. TSC1-floxed mice (TSC1flox/flox) were crossed with Prrx1-Cre or BGLAP-Cre transgenic mice or mesenchymal stem cell- and osteoblast-specific TSC1-deficient mice, respectively. Somatic and vertebral differences between WT and Prrx1-TSC1 null mice were examined at 4 weeks after birth. Results. No apparent body size abnormalities were apparent in newborn and 4-week- to 2-month-old mice with BGLAP-Cre driver-depleted TSC1. Vertebral and intervertebral discs displayed strong dysplasia in Prrx1-TSC1 null mice. In contrast, vertebrae were only slightly affected, and intervertebral discs from skeletal preparations displayed no apparent changes in BGLAP-TSC1 null mice. Conclusion. Our data suggest that the TSC1 gene is crucial for endochondral ossification during postnatal spine development but plays discriminative roles at different stages. Mesenchymal stem cell-specific ablation of TSC1 led to severe spinal dysplasia at early stages of endochondral ossification while osteoblast-specific deletion of TSC1 affected vertebrae slightly and had no detectable effects on intervertebral discs.

scholarly journals The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination

Oncogene ◽  
2000 ◽  
Vol 19 (54) ◽  
pp. 6306-6316 ◽  
Author(s):  
Giovanna Benvenuto ◽  
Shaowei Li ◽  
Samantha J Brown ◽  
Richard Braverman ◽  
William C Vass ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tuberous Sclerosis ◽  
Gene Product ◽  
Tsc1 Gene

scholarly journals VEGFR Inhibitors for Uterine Metastatic Perivascular Epithelioid Tumors (PEComa) Resistant to mTOR Inhibitors. A Case Report and Review of Literature

2021 ◽  
Vol 11 ◽  
Author(s):  
Aikaterini Liapi ◽  
Patrice Mathevet ◽  
Fernanda G. Herrera ◽  
Delfyne Hastir ◽  
Apostolos Sarivalasis
Keyword(s):  
Kinase Inhibitor ◽  
Bone Biopsy ◽  
Single Agent ◽  
Bone Lesion ◽  
Mtor Inhibitors ◽  
Epithelioid Cell ◽  
Line Treatment ◽  
Second Line ◽  
Metastatic Progression ◽  
Tsc1 Gene

Uterine perivascular epithelioid cell tumors (PEComas) are rare neoplasms. PI3K/AKT/mTOR pathway upregulation is critical for their pathogenesis and is often associated with TSC1/TSC2 inactivation. Although first line mTOR inhibitors are an effective treatment, metastatic PEComas eventually progress. A 53-year-old woman presented a 4-month history of post-menopausal vaginal bleeding. Clinical and radiological examination detected a uterine mass and a single S1 bone lesion. The patient underwent a radical hysterectomy and bone biopsy. The anatomopathological evaluation concluded to an oligo-metastatic uterine PEComa. The tumor harbored a heterozygous deletion of 9q34 that contains the TSC1 gene. Concerning the primary lesion, the resection was complete and the single bone metastasis was treated with radiotherapy. Three months later, the patient presented bone, lung and subcutaneous metastatic progression. An everolimus and denosumab treatment was initiated. After 2 years of treatment, a clinically significant bone, lung and subcutaneous progression was detected. Following a literature review of the possible therapeutic options, we initiated a second line treatment by pazopanib. This treatment resulted in regression of the subcutaneous lesions and stability of lung and bone metastases. In this challenging, rare setting, our report suggests single agent, anti-angiogenic, tyrosine kinase inhibitor to be effective as second line treatment of metastatic uterine PEComa progressing on mTOR inhibitors.

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