Mutação constitucional do controle difuso no Brasil? Uma análise do papel do Senado Federal diante do art. 52, X, da Constituição

O objetivo do presente estudo é testar a plausibilidade da tese de que teria ocorrido mutação constitucional no sistema de controle de constitucionalidade no Brasil, especificamente quanto à competência conferida pela Constituição ao Senado Federal para suspender a eficácia de lei ou ato normativo declarado inconstitucional no controle difuso de constitucionalidade. Esse argumento foi empregado pelo Ministro Gilmar Mendes, do Supremo Tribunal Federal, no julgamento da Reclamação 4335-5/AC. Para analisar a consistência dessa tese, (a) discutiu-se as condições necessárias à plausibilidade de um argumento de mutação constitucional na ordem jurídica brasileira e (b) realizou-se uma análise empírica do papel do Senado Federal diante do art. 52, X da Constituição. Feita a coleta de dados, e aplicado o conceito de mutação constitucional sobre eles, concluiu-se que não merece prosperar a tese do Min. Gilmar Mendes em que defende o reconhecimento de “autêntica mutação constitucional” do art. 52, X da Constituição Federal. Como resultado, defende se não ser possível dar plausibilidade a esse tipo de argumentação apenas tendo por base jurisprudência, doutrina e argumentação tipicamente constitucional, necessitando de base empírica que o permita atribuir mais solidez e consistência a qualquer argumento de mutação constitucional na ordem jurídica brasileira.

A mutação constitucional como realização de defesa da Constituição da República Federativa do Brasil de 1988

O objetivo do presente trabalho é analisar a plausividade da tese da mutação constitucional como mecanismo de efetivação da Constituição da República Federativa Brasil de 1988 e a partir dos 6 (seis) principais julgados do Supremo Tribunal Federal verificar se os limites impostos a esse fenômeno estão sendo respeitados. Com objetivo de comprovar esta tese foi estudado desde a opção do poder constituinte originário em atribuir aspecto rígido a Constituição pátria, permitindo que algumas matérias de seu texto através de mecanismos específicos possam ser alterados, até a legitimidade reflexa dos ministros do STF para atuarem como legisladores positivos alterando o sentido da norma sem modificação de seu conteúdo. A exposição dos limites impostos a mutação constitucional também foi alvo de especial destaque, pois somente a partir da compreensão destes seria possível uma análise sobre eventual extrapolação de competência do Poder Judiciário. A partir dos julgados do STF verificamos que a mutação constitucional está sendo aplicada dentro os limites impostos, logo este instituto atingiu seu objetivo central de aproximar as normas constitucionais a realidade da sociedade sem ferir o princípio da Separação de Poderes. Como resultado concluímos que a mutação constitucional a partir do cenário político atual que assume a asfixia e a consequente morosidade do Poder Legislativo, é um instrumento imprescindível para dar efetividade aos preceitos e princípios fundamentais da Constituição. Na atual conjuntura abdicar deste valioso instrumento seria o mesmo que assumir o fracasso e a inobservância de todo ordenamento jurídico, já que este não conseguirá reger as relações humanas da sociedade.

A objetivação do controle concreto de constitucionalidade nas decisões do Supremo Tribunal Federal

The independence of the United States and the revolutions that emerged in Europe in the eighteenth century led to the birth of the written constitution, with a mission to limit the power of the State and to ensure fundamental rights to citizens. Thus, the Constitution has become the norm and ultimate founding of the State. Because of this superiority felt the need to protect her, emerging from that constitutional jurisdiction, taking control of constitutionality of provisions his main instrument. In Brazil, the constitutionality control began with the Constitution of 1891, when "imported" the American model, which is named after incidental diffuse model of judicial review. Indeed, allowed that any judge or court could declare the unconstitutionality of the law or normative act in a concrete case. However, the Brazilian Constituent did not bring the U.S. Institute of stare decisis, by which the precedents of higher courts eventually link the below. Because of this lack, each tribunal Brazilian freely decide about the constitutionality of a rule, so that the decision took effect only between the parties to the dispute. This prompted the emergence of conflicting decisions between judicantes organs, which ultimately undermine legal certainty and the image of the judiciary. As a solution to the problem, was incorporated from the 1934 Constitution to rule that the Senate would suspend the law declared unconstitutional by the Supreme Court. With the introduction of abstract control of constitutionality, since 1965, the Supreme Court went on to also have the power to declare the invalidity of the provision unconstitutional, effectively against all without the need for the participation of the Senate. However, it remained the view that in case the Supreme Court declared the unconstitutionality of the fuzzy control law by the Senate would continue with the competence to suspend the law unconstitutional, thus the decision of the Praetorium Exalted restricted parties. The 1988 Constitution strengthened the abstract control expanding legitimized the Declaratory Action of Unconstitutionality and creating new mechanisms of abstract control. Adding to this, the Constitutional Amendment. No. 45/2004 brought the requirement of general repercussion and created the Office of Binding Precedent, both to be applied by the Supreme Court judgments in individual cases, thus causing an approximation between the control abstract and concrete constitutional. Saw themselves so that the Supreme Court, to be the guardian of the Constitution, its action should be directed to the trial of issues of public interest. In this new reality, it becomes more necessary the participation of the Senate to the law declared unconstitutional in fuzzy control by the Supreme Court can reach everyone, because such an interpretation has become obsolete. So, to adapt it to this reality, such a rule must be read in the sense that the Senate give publicity to the law declared unconstitutional by the Supreme Court, since mutated constitutional

A mutação jurisprudencial da constituição em diálogo

O presente estudo tem por objetivo analisar o fenômeno da mutação da Constituição quando reconhecida pelo Tribunal Constitucional. O estudo se inicia de uma perspectiva mais ampla, que analisa a evolução do conceito da mutação constitucional na doutrina, dentro do universo da doutrina europeia continental, e posiciona-se acerca da concepção de mutação jurisprudencial da Constituição, que parece mais adequada a funcionar como um fio condutor de distribuição de competências no âmbito da concretização do significado constitucional. Em seguida, procura-se demonstrar que a mutação jurisprudencial da Constituição funciona, ao mesmo tempo, como meio de integração e controle das demais mutações, que ganham uma forma concreta e formal. Pretende-se apresentar a decisão do Tribunal como uma síntese formal do diálogo entre as dimensões da faticidade e da normatividade de forma a fomentar o sentimento constitucional. Por fim, com a intenção de propor alguma solução para eventuais tensões e desacordos presentes entre as mutações formalizadas pelo Tribunal Constitucional e o legislador constituinte, acerca de quem deveria juridicamente dar a última palavra em matéria do significado constitucional, investiga-se a chamada doutrina do diálogo constitucional, surgida na América e no Canadá, que tem tomado um enorme fôlego nos últimos anos e pretende oferecer um caminho intermediário, de forma a demonstrar que os atores constitucionais, cada um dentro do seu papel e dos seus limites de atuação, constroem juntos o verdadeiro significado constitucional, devendo a legitimidade democrática ser vista de um ponto de vista circular e material e não linear e formal.

Novel inactivating mutations in the GH secretagogue receptor gene in patients with constitutional delay of growth and puberty

Background: A limited number of mutations in the GH secretagogue receptor gene (GHSR) have been described in patients with short stature. Objective: To analyze GHSR in idiopathic short stature (ISS) children including a subgroup of constitutional delay of growth and puberty (CDGP) patients. Subjects and methods: The GHSR coding region was directly sequenced in 96 independent patients with ISS, 31 of them with CDGP, in 150 adults, and in 197 children with normal stature. The pharmacological consequences of GHSR non-synonymous variations were established using in vitro cell-based assays. Results: Five different heterozygous point variations in GHSR were identified (c.-6 G>C, c.251G>T (p.Ser84Ile), c.505G>A (p.Ala169Thr), c.545 T>C (p.Val182Ala), and c.1072G>A (p.Ala358Thr)), all in patients with CDGP. Neither these allelic variants nor any other mutations were found in 694 alleles from controls. Functional studies revealed that two of these variations (p.Ser84Ile and p. Val182Ala) result in a decrease in basal activity that was in part explained by a reduction in cell surface expression. The p.Ser84Ile mutation was also associated with a defect in ghrelin potency. These mutations were identified in two female patients with CDGP (at the age of 13 years, their height SDS were -2.4 and -2.3). Both patients had normal progression of puberty and reached normal adult height (height SDS of -0.7 and -1.4) without treatment. Conclusion: This is the first report of GHSR mutations in patients with CDGP. Our data raise the intriguing possibility that abnormalities in ghrelin receptor function may influence the phenotype of individuals with CDGP.

Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia

Loss-of-function mutations in telomerase complex genes can cause bone marrow failure, dyskeratosis congenita, and acquired aplastic anemia, both diseases that predispose to acute myeloid leukemia. Loss of telomerase function produces short telomeres, potentially resulting in chromosome recombination, end-to-end fusion, and recognition as damaged DNA. We investigated whether mutations in telomerase genes also occur in acute myeloid leukemia. We screened bone marrow samples from 133 consecutive patients with acute myeloid leukemia and 198 controls for variations in TERT and TERC genes. An additional 89 patients from a second cohort, selected based on cytogenetic status, and 528 controls were further examined for mutations. A third cohort of 372 patients and 384 controls were specifically tested for one TERT gene variant. In the first cohort, 11 patients carried missense TERT gene variants that were not present in controls (P<0.0001); in the second cohort, TERT mutations were associated with trisomy 8 and inversion 16. Mutation germ-line origin was demonstrated in 5 patients from whom other tissues were available. Analysis of all 3 cohorts (n = 594) for the most common gene variant (A1062T) indicated a prevalence 3 times higher in patients than in controls (n = 1,110; P = 0.0009). Introduction of TERT mutants into telomerase-deficient cells resulted in loss of enzymatic activity by haploinsufficiency. Inherited mutations in TERT that reduce telomerase activity are risk factors for acute myeloid leukemia. We propose that short and dysfunctional telomeres limit normal stem cell proliferation and predispose for leukemia by selection of stem cells with defective DNA damage responses that are prone to genome instability.

Constitutional Telomerase Mutations Are Genetic Risk Factors for Cirrhosis

Some patients with liver disease progress to cirrhosis, but the risk factors for cirrhosis development are unknown. Dyskeratosis congenita, an inherited bone marrow failure syndrome associated with mucocutaneous anomalies, pulmonary fibrosis, and cirrhosis, is caused by germline mutations of genes in the telomerase complex. We examined whether telomerase mutations also occurred in sporadic cirrhosis. In all, 134 patients with cirrhosis of common etiologies treated at the Liver Research Institute, University of Arizona, between May 2008 and July 2009, and 528 healthy subjects were screened for variation in the TERT and TERC genes by direct sequencing; an additional 1,472 controls were examined for the most common genetic variation observed in patients. Telomere length of leukocytes was measured by quantitative polymerase chain reaction. Functional effects of genetic changes were assessed by transfection of mutation-containing vectors into telomerase-deficient cell lines, and telomerase activity was measured in cell lysates. Nine of the 134 patients with cirrhosis (7%) carried a missense variant in TERT, resulting in a cumulative carrier frequency significantly higher than in controls (P = 0.0009). One patient was homozygous and eight were heterozygous. The allele frequency for the most common missense TERT variant was significantly higher in patients with cirrhosis (2.6%) than in 2,000 controls (0.7%; P = 0.0011). One additional patient carried a TERC mutation. The mean telomere length of leukocytes in patients with cirrhosis, including six mutant cases, was shorter than in age-matched controls (P = 0.0004). Conclusion: Most TERT gene variants reduced telomerase enzymatic activity in vitro. Loss-of-function telomerase gene variants associated with short telomeres are risk factors for sporadic cirrhosis. (HEPATOLOGY 2011;53:1600-1607)

A novel homozygous splice acceptor site mutation of KISS1R in two siblings with normosmic isolated hypogonadotropic hypogonadism

Context: Loss-of-function mutations of the kisspeptin-1 receptor gene, KISS1R, have been identified in patients with normosmic isolated hypogonadotropic hypogonadism (nIHH). Objective: To investigate KISS1R defects in patients with absent or delayed puberty. Patients: We investigated KISS1R gene defects in a cohort of 99 Brazilian patients with nIHH or constitutional delay of puberty (CDP). Methods: The entire coding region of KISS1R was amplified by PCR followed by automatic sequencing. In addition, screening for KISS1R exonic deletions was performed by multiplex ligation-dependent probe amplification. Results: One novel homozygous KISS1R mutation was identified in two siblings with nIHH. This variant was an insertion/deletion (indel) mutation characterized by the deletion of three nucleotides (GCA) at position -2 to -4, and by the insertion of seven nucleotides (ACCGGCT) at the same position, within the 30 splice acceptor site of intron 2 of KISS1R. The brothers who carried this KISS1R mutation had no clinical evidence of pubertal development at the ages of 14 and 20 years. Computational analysis of this indel mutation predicted the generation of an abnormal protein. In addition, a new heterozygous KISS1R variant (p.E252Q) was identified in a male patient with sporadic nIHH. However, in vitro studies of this variant did not demonstrate functional impairment. Only known polymorphisms were identified in patients with CDP. Conclusion: Loss-of-function mutations of KISS1R represents a rare cause of nIHH, and was absent in patients with CDP. We have described a novel KISS1R homozygous splice acceptor site mutation in the familial form of nIHH.

Homozygous Inactivating Mutation In Nanos3 In Two Sisters With Primary Ovarian Insufficiency.

Despite the increasing understanding of female reproduction, the molecular diagnosis of primary ovarian insufficiency (POI) is seldom obtained. The RNA-binding protein NANOS3 poses as an interesting candidate gene for POI since members of the Nanos family have an evolutionarily conserved function in germ cell development and maintenance by repressing apoptosis. We performed mutational analysis of NANOS3 in a cohort of 85 Brazilian women with familial or isolated POI, presenting with primary or secondary amenorrhea, and in ethnically-matched control women. A homozygous p.Glu120Lys mutation in NANOS3 was identified in two sisters with primary amenorrhea. The substituted amino acid is located within the second C2HC motif in the conserved zinc finger domain of NANOS3 and in silico molecular modelling suggests destabilization of protein-RNA interaction. In vitro analyses of apoptosis through flow cytometry and confocal microscopy show that NANOS3 capacity to prevent apoptosis was impaired by this mutation. The identification of an inactivating missense mutation in NANOS3 suggests a mechanism for POI involving increased primordial germ cells (PGCs) apoptosis during embryonic cell migration and highlights the importance of NANOS proteins in human ovarian biology.

Familial Systemic Mastocytosis With Germline Kit K509i Mutation Is Sensitive To Treatment With Imatinib, Dasatinib And Pkc412.

Mastocytosis are myeloproliferative neoplasms commonly related to gain-of-function mutations involving the tyrosine kinase domain of KIT. We herein report a case of familial systemic mastocytosis with the rare KIT K509I germ line mutation affecting two family members: mother and daughter. In vitro treatment with imatinib, dasatinib and PKC412 reduced cell viability of primary mast cells harboring KIT K509I mutation. However, imatinib was more effective in inducing apoptosis of neoplastic mast cells. Both patients with familial systemic mastocytosis had remarkable hematological and skin improvement after three months of imatinib treatment, suggesting that it may be an effective front line therapy for patients harboring KIT K509I mutation.

Pyrimidine-5'-nucleotidase Campinas, A New Mutation (p.r56g) In The Nt5c3 Gene Associated With Pyrimidine-5'-nucleotidase Type I Deficiency And Influence Of Gilbert's Syndrome On Clinical Expression.

Pyrimidine-5'-nucleotidase type I (P5'NI) deficiency is an autosomal recessive condition that causes nonspherocytic hemolytic anemia, characterized by marked basophilic stippling and pyrimidine nucleotide accumulation in erythrocytes. We herein present two African descendant patients, father and daughter, with P5'N deficiency, both born from first cousins. Investigation of the promoter polymorphism of the uridine diphospho glucuronosyl transferase 1A (UGT1A) gene revealed that the father was homozygous for the allele (TA7) and the daughter heterozygous (TA6/TA7). P5'NI gene (NT5C3) gene sequencing revealed a further change in homozygosity at amino acid position 56 (p.R56G), located in a highly conserved region. Both patients developed gallstones; however the father, who had undergone surgery for the removal of stones, had extremely severe intrahepatic cholestasis and, liver biopsy revealed fibrosis and siderosis grade III, leading us to believe that the homozygosity of the UGT1A polymorphism was responsible for the more severe clinical features in the father. Moreover, our results show how the clinical expression of hemolytic anemia is influenced by epistatic factors and we describe a new mutation in the P5'N gene associated with enzyme deficiency, iron overload, and severe gallstone formation. To our knowledge, this is the first description of P5'N deficiency in South Americans.

Preserved Fertility In A Patient With Gynecomastia Associated With The P.pro695ser Mutation In The Androgen Receptor.

The androgen insensitivity syndrome (AIS) is described as a dysfunction of the androgen receptor (AR) in 46,XY individuals, which can be associated with mutations in the AR gene or can be due to unknown mechanisms. Different mutations in AIS generally cause variable phenotypes that range from a complete hormone resistance to a mild form usually associated with male infertility. The purpose of this study was to search for mutations in the AR gene in a fertile man with gynecomastia and to evaluate the influence of the mutation on the AR transactivation ability. Sequencing of the AR gene revealed the p.Pro695Ser mutation. It is located within the AR ligand-binding domain. Bioinformatics analysis indicated a deleterious role, which was verified after testing transactivation activity and N-/C-terminal (N/C) interaction by in vitro expression of a reporter gene and 2-hybrid assays. p.Pro695Ser showed low levels of both transactivation activity and N/C interaction at low dihydrotestosterone (DHT) conditions. As the ligand concentration increased, both transactivation activity and N/C interaction also increased and reached normal levels. Therefore, this study provides functional insights for the p.Pro695Ser mutation described here for the first time in a patient with mild AIS. The expression profile of p.Pro695Ser not only correlates to the patient's phenotype, but also suggests that a high-dose DHT therapy may overcome the functional deficit of the mutant AR.

The G209A mutation in the alpha-synuclein gene in Brazilian families with Parkinson's disease

A missense G209A mutation of the alpha-synuclein gene was recently described in a large Contursi kindred with Parkinson's disease (PD). The objective of this study is to determine if the mutation G209A of the alpha-synuclein gene was present in 10 Brazilian families with PD. PD patients were recruited from movement disorders clinics of Brazil. A family history with two or more affected in relatives was the inclusion criterion for this study. The alpha-synuclein G209A mutation assay was made using polymerase chain reaction and the restriction enzyme Tsp45I. Ten patients from 10 unrelated families were studied. The mean age of PD onset was 42.7 years old. We did not find the G209A mutation in our 10 families with PD. Our results suggest that alpha-synuclein mutation G209A is uncommon in Brazilian PD families.