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1.
Brain ; 146(3): 858-864, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36417180

RESUMO

Pyruvate is an essential metabolite produced by glycolysis in the cytosol and must be transported across the inner mitochondrial membrane into the mitochondrial matrix, where it is oxidized to fuel mitochondrial respiration. Pyruvate import is performed by the mitochondrial pyruvate carrier (MPC), a hetero-oligomeric complex composed by interdependent subunits MPC1 and MPC2. Pathogenic variants in the MPC1 gene disrupt mitochondrial pyruvate uptake and oxidation and cause autosomal-recessive early-onset neurological dysfunction in humans. The present work describes the first pathogenic variants in MPC2 associated with human disease in four patients from two unrelated families. In the first family, patients presented with antenatal developmental abnormalities and harboured a homozygous c.148T>C (p.Trp50Arg) variant. In the second family, patients that presented with infantile encephalopathy carried a missense c.2T>G (p.Met1?) variant disrupting the initiation codon. Patient-derived skin fibroblasts exhibit decreased pyruvate-driven oxygen consumption rates with normal activities of the pyruvate dehydrogenase complex and mitochondrial respiratory chain and no defects in mitochondrial content or morphology. Re-expression of wild-type MPC2 restored pyruvate-dependent respiration rates in patient-derived fibroblasts. The discovery of pathogenic variants in MPC2 therefore broadens the clinical and genetic landscape associated with inborn errors in pyruvate metabolism.


Assuntos
Mitocôndrias , Proteínas de Transporte da Membrana Mitocondrial , Humanos , Feminino , Gravidez , Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Mitocôndrias/metabolismo , Transporte Biológico , Ácido Pirúvico/metabolismo
2.
J Ultrasound Med ; 43(2): 411-414, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37929614

RESUMO

Primrose syndrome is a very rare congenital malformation. Symptoms of this disorder may appear during childhood, but the diagnosis is identified in adulthood in the majority of cases. The prenatal diagnosis of Primrose syndrome is not developed in the literature. We present herein a case series of 3 cases with characteristic sonographic features. A dysmorphic metopic suture, downslanting palpebral fissures, a wide forehead, and agenesis of corpus callosum are the main signs. A missense mutation in ZBTB20 identified in whole exome sequencing can confirm the prenatal diagnosis of Primrose syndrome.


Assuntos
Anormalidades Múltiplas , Calcinose , Otopatias , Deficiência Intelectual , Atrofia Muscular , Gravidez , Feminino , Humanos , Anormalidades Múltiplas/diagnóstico por imagem , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Diagnóstico Pré-Natal , Agenesia do Corpo Caloso/diagnóstico por imagem , Agenesia do Corpo Caloso/genética
3.
Am J Med Genet A ; 182(3): 565-569, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793730

RESUMO

RING Finger Protein 113 A (RNF113A, MIM 300951) is a highly conserved gene located on chromosome Xq24-q25, encoding a protein containing two conserved zinc finger domains involved in DNA alkylation repair and premessenger RNA splicing. To date, only one pathogenic variant of RNF113A, namely c.901C>T; p.Gln301Ter, has been reported in humans by Tarpey et al. in 2009. Thereafter, Corbett et al. stated that this variant was responsible for an X-linked form of nonphotosensitive trichothiodystrophy associated with profound intellectual disability, microcephaly, partial corpus callosum agenesis, microphallus, and absent or rudimentary testes. This variant was then shown to alter DNA alkylation repair, providing an additional argument supporting its pathogenicity and important clues about the underlying pathophysiology of nonphotosensitive trichothiodystrophy. Using exome sequencing, we identified exactly the same RNF113A variant in two fetuses affected with abnormalities similar to those previously reported by Corbett et al. To our knowledge, this is the second report of a RNF113A pathogenic variant in humans.


Assuntos
Agenesia do Corpo Caloso/genética , Proteínas de Ligação a DNA/genética , Deficiência Intelectual/genética , Síndromes de Tricotiodistrofia/genética , Agenesia do Corpo Caloso/diagnóstico , Agenesia do Corpo Caloso/patologia , Exoma/genética , Feminino , Genes Ligados ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/patologia , Masculino , Microcefalia/diagnóstico , Microcefalia/genética , Microcefalia/patologia , Linhagem , Síndromes de Tricotiodistrofia/diagnóstico , Síndromes de Tricotiodistrofia/patologia , Sequenciamento do Exoma
4.
Am J Med Genet A ; 173(3): 706-711, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28168853

RESUMO

EPG5-related Vici syndrome is a rare multisystem autosomal recessive disorder characterized by corpus callosum agenesis (ACC), hypopigmentation, cataracts, acquired microcephaly, failure to thrive, cardiomyopathy and profound developmental delay, and immunodeficiency. We report here the first case of prenatally diagnosed Vici syndrome with delayed gyration associated with ACC. Trio based exome sequencing allowed the identification of a compound heterozygous mutation in the EPG5 gene. Our patient subsequently demonstrated severe developmental delay, hypopigmentation, progressive microcephaly, and failure to thrive which led to suspicion of the diagnosis. Her MRI demonstrated ACC with frontoparietal polymicrogyria, severe hypomyelination, and pontocerebellar atrophy. This prenatal presentation of malformations of cortical development in combination with ACC expands the EPG5-related phenotypic spectrum. Our report supports the idea that EPG5-related Vici syndrome is both a neurodevelopmental and neurodegenerative disorder. © 2017 Wiley Periodicals, Inc.


Assuntos
Agenesia do Corpo Caloso/diagnóstico , Agenesia do Corpo Caloso/genética , Mutação , Fenótipo , Polimicrogiria/diagnóstico , Polimicrogiria/genética , Proteínas/genética , Proteínas Relacionadas à Autofagia , Exoma , Feminino , Estudos de Associação Genética , Testes Genéticos , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Proteínas de Membrana Lisossomal , Imageamento por Ressonância Magnética , Masculino , Gravidez , Diagnóstico Pré-Natal , Ultrassonografia , Proteínas de Transporte Vesicular
5.
Fetal Diagn Ther ; 42(2): 137-143, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27794580

RESUMO

BACKGROUND: There is no precise prenatal indicator to refine an accurate prognosis in case of sacral agenesis and to define the diagnostic approach and outcome criteria in case of fetal sacral agenesis using 3 characteristics of the conus medullaris (CM): its position, its appearance, and associated spinal abnormalities. METHODS: Ten cases of prenatally diagnosed sacral agenesis were included between 1995 and 2014 after collating ultrasound findings and prenatal computed tomography data. RESULTS: Two cases of total sacral agenesis and 8 of partial agenesis were included. There were 1 or more spinal abnormalities in 8/10 cases: 6 lipomas, 4 low-lying tethered cords, 2 diastematomyelias, and 1 syringomyelia. Three situations were distinguished: sacral agenesis with low-lying tethered cord, sacral agenesis with a truncated CM, and sacral agenesis with CM in place. If the sacral agenesis is isolated, a lipoma should be sought. Lipomas of the filum have a good prognosis, whereas lipomas of the CM cause neurological deficits in 1/3 of cases. When there is a low-lying tethered cord, a diastematomyelia or a syringomyelia may be associated. In truncated CM, there may be a severe form suggestive of caudal regression syndrome. Serious ultrasound signs are immobility of the lower limbs, talipes equinovarus, impaired bladder emptying, and dilatation of the upper urinary tract. CONCLUSION: A precise description of the morphology of the CM, its position, and associated spinal malformations are important in defining the neurological, urinary, gastrointestinal, and motor functions prognosis in cases of fetal sacral agenesis.


Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Meningocele/diagnóstico por imagem , Região Sacrococcígea/anormalidades , Medula Espinal/diagnóstico por imagem , Ultrassonografia Pré-Natal , Feminino , Idade Gestacional , Humanos , Masculino , Gravidez , Região Sacrococcígea/diagnóstico por imagem
6.
Fetal Diagn Ther ; 40(3): 187-194, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26820669

RESUMO

OBJECTIVE: The objective of this study was to determine the frequency and the nature of associated anomalies, especially malformations and chromosome abnormalities, in a population of fetuses with an aberrant right subclavian artery (ARSA). MATERIALS AND METHODS: This is a 7-year descriptive study. All patients whose fetus had an ARSA diagnosed by ultrasound performed during the 1st, 2nd, or 3rd trimester of pregnancy were included, regardless of their risk of chromosomal abnormalities. RESULTS: Between May 2007 and April 2014, an ARSA was diagnosed in 120 fetuses. The outcome was found in 108 cases (90%). ARSA was an isolated finding in 54/108 cases (50%). In 20% (22/108) of the fetuses, chromosomal abnormalities were detected. No chromosomal abnormalities were found in fetuses with an isolated ARSA. 82% (18/22) of chromosomal abnormalities were usual, such as trisomies 21 and 18, monosomy X, and 22q11.2 deletion. 21% (23/108) of the fetuses presenting an ARSA were associated with having a congenital heart disease. CONCLUSION: The presence of an isolated ARSA is a condition rarely associated with a chromosomal abnormality. The decision to perform an invasive karyotyping procedure under such circumstances or not may be made according to the principle of parental autonomy after extensive counselling and mostly a thorough assessment of the fetus.


Assuntos
Aneurisma/diagnóstico por imagem , Anormalidades Cardiovasculares/diagnóstico por imagem , Transtornos de Deglutição/diagnóstico por imagem , Artéria Subclávia/anormalidades , Adulto , Aneurisma/complicações , Aneurisma/genética , Anormalidades Cardiovasculares/complicações , Anormalidades Cardiovasculares/genética , Aberrações Cromossômicas , Transtornos de Deglutição/complicações , Transtornos de Deglutição/genética , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/patologia , Humanos , Cariotipagem , Gravidez , Artéria Subclávia/diagnóstico por imagem , Ultrassonografia Pré-Natal
7.
J Ultrasound Med ; 31(10): 1675-80, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23011631

RESUMO

The pituitary gland is crucially important in the function of the endocrine axis. So far, antenatal depiction of the pituitary gland was possible only using magnetic resonance imaging. We describe antenatal visualization of the pituitary gland using 2- and 3-dimensional sonography. The appearance of the gland on sonography seems to be superior compares to prenatal magnetic resonance imaging. In cases with midline anomalies of the brain, face, or cranium, depiction of the pituitary gland is feasible and recommended.


Assuntos
Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Hipófise/anatomia & histologia , Hipófise/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Feminino , Humanos
8.
Am J Obstet Gynecol ; 205(6): e6-8, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22000898

RESUMO

Using prenatal BACs-on-Beads technology, the first prenatal case of Williams-Beuren syndrome (WBS) was diagnosed. In light of this result, an ultrasound scan confirmed the presence of well-characterized features of WBS. This case report emphasizes the fact that new genomic technologies will generate prenatal information and provide helpful additional information.


Assuntos
Testes Genéticos/métodos , Diagnóstico Pré-Natal/métodos , Síndrome de Williams/diagnóstico por imagem , Síndrome de Williams/genética , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/genética , Feminino , Humanos , Fenótipo , Gravidez , Ultrassonografia , Adulto Jovem
9.
J Gynecol Obstet Hum Reprod ; 47(9): 481-485, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29932991

RESUMO

Congenital ventricular aneurysms and diverticula are rare congenital heart diseases, currently accessible to prenatal diagnosis. Information on the natural course of ventricular aneurysm or diverticulum detected during fetal life is limited as there are only few case reports and case series enumerating the defect. We aimed to describe through three cases, the prenatal features and clinical outcomes of fetal cardiac aneurysms. The first one was diagnosed during the second trimester and spontaneous evolution was favorable. The two others were diagnosed in the first trimester with a large and early pericardial effusion. For one, the parents opted for termination of pregnancy at 15 weeks of gestation and the other showed a spontaneous regression of the effusion and no hemodynamic compromise.


Assuntos
Doenças Fetais/diagnóstico por imagem , Aneurisma Cardíaco/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Derrame Pericárdico/diagnóstico por imagem , Adulto , Ecocardiografia , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Ultrassonografia Pré-Natal
10.
Am J Obstet Gynecol ; 195(5): 1379-87, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16723105

RESUMO

OBJECTIVE: Recent studies have reported the efficacy of first-trimester combined screening for Down syndrome based on maternal age, serum markers (human chorionic gonadotropin, pregnancy-associated plasma protein A), and ultrasound measurement of fetal nuchal translucency. However, those do not incorporate the value of the widely accepted routine 20-22 weeks' anomaly scan. STUDY DESIGN: We carried out a multicenter, interventional study in the unselected population of a single health authority in order to assess the performance of first-trimester combined screening, followed by routine second trimester ultrasound examination and/or screening by maternal serum markers (free beta-hCG and alpha-fetoprotein measurement or total hCG, alpha-fetoprotein, and unconjugated estriol measurement) when incidentally performed. Detection and screen positive rates were estimated using a correction method for nonverified issues. A cost analysis was also performed. RESULTS: During the study period, 14,934 women were included. Fifty-one cases of Down syndrome were observed, giving a prevalence of 3.4 per 1000 pregnancies. Of these, 46 were diagnosed through first (n = 41) or second (n = 5) trimester screening. Among the 5 screen-negative Down syndrome cases, all were diagnosed postnatally after an uneventful pregnancy. Detection and screen positive rates of first-trimester combined screening were 79.6% and 2.7%, respectively. These features reached 89.7%, and 4.2%, respectively, when combined with second-trimester ultrasound screening. The average cost of the full screening procedure was 108 euros (120 dollars) per woman and the cost per diagnosed Down syndrome pregnancy was 7,118 euros (7909 dollars). CONCLUSION: Our findings suggest that 1 pragmatic interventional 2-step approach using first-trimester combined screening followed by second-trimester detailed ultrasound examination is a suitable and acceptable option for Down syndrome screening in pregnancy.


Assuntos
Síndrome de Down/diagnóstico , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal , Adulto , Síndrome de Down/epidemiologia , Feminino , Custos de Cuidados de Saúde , Humanos , Gravidez , Diagnóstico Pré-Natal/economia , Diagnóstico Pré-Natal/normas , Prevalência , Ultrassonografia Pré-Natal/economia , Ultrassonografia Pré-Natal/normas
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