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1.
Nat Commun ; 11(1): 4752, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958754

RESUMO

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH-secreting pituitary tumors over-expressing the orphan G-protein coupled receptor, GPR101. The role of GPR101 in GH secretion remains obscure. We studied GPR101 signaling pathways and their effects in HEK293 and rat pituitary GH3 cell lines, human tumors and in transgenic mice with elevated somatotrope Gpr101 expression driven by the rat Ghrhr promoter (GhrhrGpr101). Here, we report that Gpr101 causes elevated GH/prolactin secretion in transgenic GhrhrGpr101 mice but without hyperplasia/tumorigenesis. We show that GPR101 constitutively activates not only Gs, but also Gq/11 and G12/13, which leads to GH secretion but not proliferation. These signatures of GPR101 signaling, notably PKC activation, are also present in human pituitary tumors with high GPR101 expression. These results underline a role for GPR101 in the regulation of somatotrope axis function.


Assuntos
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Gigantismo/metabolismo , Hormônio do Crescimento/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Acromegalia/metabolismo , Acromegalia/patologia , Animais , Composição Corporal , Linhagem Celular , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Gigantismo/patologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Hipófise/metabolismo , Proteína Quinase C/metabolismo , Ratos , Receptores Acoplados a Proteínas-G/genética
2.
J Clin Neurosci ; 78: 420-422, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32336638

RESUMO

Gigantism (early-onset acromegaly) is a rare pediatric disorder caused by a growth hormone (GH)-secreting pituitary adenoma. Approximately 50% patients of gigantism have a germline mutation, most commonly an inactivating mutation in the aryl-hydrocarbon interacting receptor protein (AIP) gene on chromosome 11q13.2. We present an 11-year-old male patient with a GH-secreting pituitary macroadenoma who presented with excessive growth spurts, behavioral changes, and frontal headaches. He was successfully treated with an endoscopic endonasal gross total resection and subsequently demonstrated biochemical cure. Whole-exome sequencing showed a heterozygous germline mutation in the AIP gene suggesting pituitary adenoma predisposition. Analysis of the tumor tissue revealed a large-scale deletion on chromosome 11 overlapping with AIP leading to bi-allelic AIP loss. Coincident germline and somatic AIP mutations were likely causal in formation of a GH-secreting adenoma with an aggressive phenotype. This case exemplifies the need for early diagnosis and curative surgery in the management of AIP-mutated pituitary adenomas.


Assuntos
Mutação em Linhagem Germinativa , Gigantismo/etiologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Hipofisárias/patologia , Criança , Cromossomos Humanos Par 11/genética , Gigantismo/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Heterozigoto , Humanos , Masculino , Fenótipo , Neoplasias Hipofisárias/genética , Deleção de Sequência
3.
Eur. j. anat ; 24(2): 155-159, mar. 2020. ilus
Artigo em Inglês | IBECS | ID: ibc-191243

RESUMO

Hemimegalencephaly is a rare disorder which may present alone or be associated with hemicorporal gigantism. However, an association with crossed hemicorporal gigantism involving different upper and lower halves of the body along with selective visceromegaly is, so far, unreported in literature.A 14-year-old male presented with a crossed variety of hemigigantism associated with a mild form of hemimegalencephaly affecting the left cer-ebral and cerebellar hemispheres. On ultrasound, left renomegaly was noted, though no pathology or dysfunction of the organ could be demonstrated. This case merited a report due to an unusual presentation that defies explanations offered so far for the condition


No disponible


Assuntos
Humanos , Masculino , Adolescente , Hemimegalencefalia/diagnóstico por imagem , Gigantismo/diagnóstico , Hiperplasia
4.
Eur J Endocrinol ; 182(2): 139-147, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31751304

RESUMO

Context: Patients with tall stature often remain undiagnosed after clinical investigation and few studies have genetically assessed this group, most of them without a systematic approach. Objective: To assess prospectively a group of individuals with tall stature, with and without syndromic features, and to establish a molecular diagnosis for their growth disorder. Design: Screening by karyotype (n = 42), chromosome microarray analyses (CMA) (n = 16), MS-MLPA (n = 2) targeted panel (n = 12) and whole-exome sequencing (n = 31). Patients and methods: We selected 42 patients with tall stature after exclusion of pathologies in GH/IGF1 axis and divided them into syndromic (n = 30) and non-syndromic (n = 12) subgroups. Main outcome measures: Frequencies of pathogenic findings. Results: We identified two patients with chromosomal abnormalities including SHOX trisomy by karyotype, one 9q22.3 microdeletion syndrome by CMA, two cases of Beckwith-Wiedemann syndrome by targeted MS-MLPA analysis and nine cases with heterozygous pathogenic or likely pathogenic genetic variants by multigene analysis techniques (FBN1 = 3, NSD1 = 2, NFIX = 1, SUZ12 = 1, CHD8 = 1, MC4R = 1). Three of 20 patients analyzed by WES had their diagnosis established. Only one non-syndromic patient had a definitive diagnosis. The sequential genetic assessment diagnosed 14 out of 42 (33.3%) tall patients. Conclusion: A systematic molecular approach of patients with tall stature was able to identify the etiology in 13 out of 30 (43.3%) syndromic and 1 out of 12 (8.3%) non-syndromic patients, contributing to the genetic counseling and avoiding unfavorable outcomes in the syndromic subgroup.


Assuntos
Gigantismo/genética , Transtornos do Crescimento/genética , Adolescente , Adulto , Estatura/genética , Criança , Pré-Escolar , Variações do Número de Cópias de DNA/genética , Heterozigoto , Humanos , Cariótipo , Cariotipagem , Pessoa de Meia-Idade , Estudos Prospectivos , Proteína de Homoeobox de Baixa Estatura/genética , Sequenciamento Completo do Exoma/métodos , Adulto Jovem
5.
Medicine (Baltimore) ; 98(43): e17616, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651874

RESUMO

RATIONALE: Simpson-Golabi-Behmel syndrome type 1 (SGBS1) is caused by mutations in GPC3 or in both GPC3 and GPC4. Physical manifestations of SGBS1 include fetal overgrowth and macrostomia, macroglossia. Subclinical hypothyroidism has never been reported in SGBS1 cases. PATIENT CONCERNS: An 8-days-old boy was referred to our hospital with persistent hypoglycemia and special facies. And the infant showed elevated levels of thyroid-stimulating hormone (TSH). Free T4 and free T3 were normal. DIAGNOSES: Definitive diagnosis of SGBS1 depends on clinical features and genetic testing. A nonsense mutation (c.1515C > A, p. Cys505*) was tested by whole-exome sequencing. INTERVENTIONS: Normal blood glucose levels were maintained with glucose infusions. Levothyroxine was given to the patient for treating subclinical hypothyroidism. OUTCOMES: The parents decided to abandon the treatment of the patient. We learned that the patient died of a lung infection by a telephone follow-up. LESSONS: Subclinical hypothyroidism could be added to the known clinical manifestations of SGBS1.


Assuntos
Arritmias Cardíacas/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Gigantismo/diagnóstico , Cardiopatias Congênitas/diagnóstico , Hipotireoidismo/diagnóstico , Deficiência Intelectual/diagnóstico , China , Diagnóstico Diferencial , Evolução Fatal , Humanos , Recém-Nascido , Masculino
6.
J Med Case Rep ; 13(1): 280, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31481085

RESUMO

BACKGROUND: Familial glucocorticoid deficiency is a rare autosomal recessive disorder characterized by isolated glucocorticoid deficiency. Most patients are diagnosed following episodes of hypoglycemia or convulsion. We report the case of an infant with familial glucocorticoid deficiency who presented with hyperpigmentation, gigantism, and motor developmental delay without documented hypoglycemia, convulsion, or circulatory collapse. CASE PRESENTATION: A 10-month-old Sri Lankan Sinhalese baby boy born to consanguineous parents presented with generalized hyperpigmentation and overgrowth since birth. He had marginal gross motor developmental delay. His weight, length, and head circumference were above normal range for his age. Investigations revealed low serum cortisol and high adrenocorticotrophic hormone levels with no cortisol response following adrenocorticotropin stimulation. Serum electrolytes and aldosterone levels were normal. A diagnosis of familial glucocorticoid deficiency was made based on isolated glucocorticoid deficiency, hyperpigmentation, and tall stature. CONCLUSIONS: This case report highlights that glucocorticoid deficiency can present without documented hypoglycemia and circulatory collapse and a high degree of suspicion is needed in diagnosis.


Assuntos
Insuficiência Adrenal/congênito , Insuficiência Adrenal/diagnóstico , Deficiências do Desenvolvimento/etiologia , Gigantismo/etiologia , Hiperpigmentação/etiologia , Humanos , Lactente , Masculino
7.
Arch Endocrinol Metab ; 63(4): 385-393, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365626

RESUMO

INTRODUCTION: Gigantism is a rare pediatric disease characterized by increased production of growth hormone (GH) before epiphyseal closure, that manifests clinically as tall stature, musculoskeletal abnormalities, and multiple comorbidities. MATERIALS AND METHODS: Case series of 6 male patients with gigantism evaluated at the Endocrinology Service of Hospital de San José (Bogotá, Colombia) between 2010 and 2016. RESULTS: All patients had macroadenomas and their mean final height was 2.01 m. The mean age at diagnosis was 16 years, and the most common symptoms were headache (66%) and hyperhidrosis (66%). All patients had acral changes, and one had visual impairment secondary to compression of the optic chiasm. All patients underwent surgery, and 5 (83%) required additional therapy for biochemical control, including radiotherapy (n = 4, 66%), somatostatin analogues (n = 5, 83%), cabergoline (n = 3, 50%), and pegvisomant (n = 2, 33%). Three patients (50%) achieved complete biochemical control, while 2 patients showed IGF-1 normalization with pegvisomant. Two patients were genetically related and presented a mutation in the aryl hydrocarbon receptor-interacting protein (AIP) gene (pathogenic variant, c.504G>A in exon 4, p.Trp168*), fulfilling the diagnostic criteria of familial isolated pituitary adenoma. CONCLUSIONS: This is the largest case series of patients with gigantism described to date in Colombia. Transsphenoidal surgery was the first-choice procedure, but additional pharmacological therapy was usually required. Mutations in the AIP gene should be considered in familial cases of GH-producing adenomas.


Assuntos
Adenoma/terapia , Gigantismo/terapia , Neoplasias Hipofisárias/terapia , Adenoma/diagnóstico , Adolescente , Colômbia , Seguimentos , Gigantismo/diagnóstico , Hormônio do Crescimento/sangue , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Humanos , Fator de Crescimento Insulin-Like I/análise , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Mutação/genética , Linhagem , Neoplasias Hipofisárias/diagnóstico , Estudos Retrospectivos , Distribuição por Sexo , Resultado do Tratamento , Adulto Jovem
8.
Arch. endocrinol. metab. (Online) ; 63(4): 385-393, July-Aug. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1019354

RESUMO

ABSTRACT Introduction Gigantism is a rare pediatric disease characterized by increased production of growth hormone (GH) before epiphyseal closure, that manifests clinically as tall stature, musculoskeletal abnormalities, and multiple comorbidities. Materials and methods Case series of 6 male patients with gigantism evaluated at the Endocrinology Service of Hospital de San José (Bogotá, Colombia) between 2010 and 2016. Results All patients had macroadenomas and their mean final height was 2.01 m. The mean age at diagnosis was 16 years, and the most common symptoms were headache (66%) and hyperhidrosis (66%). All patients had acral changes, and one had visual impairment secondary to compression of the optic chiasm. All patients underwent surgery, and 5 (83%) required additional therapy for biochemical control, including radiotherapy (n = 4, 66%), somatostatin analogues (n = 5, 83%), cabergoline (n = 3, 50%), and pegvisomant (n = 2, 33%). Three patients (50%) achieved complete biochemical control, while 2 patients showed IGF-1 normalization with pegvisomant. Two patients were genetically related and presented a mutation in the aryl hydrocarbon receptor-interacting protein (AIP) gene (pathogenic variant, c.504G>A in exon 4, p.Trp168*), fulfilling the diagnostic criteria of familial isolated pituitary adenoma. Conclusions This is the largest case series of patients with gigantism described to date in Colombia. Transsphenoidal surgery was the first-choice procedure, but additional pharmacological therapy was usually required. Mutations in the AIP gene should be considered in familial cases of GH-producing adenomas.


Assuntos
Humanos , Masculino , Adolescente , Adulto Jovem , Neoplasias Hipofisárias/terapia , Adenoma/terapia , Gigantismo/terapia , Linhagem , Neoplasias Hipofisárias/diagnóstico , Fator de Crescimento Insulin-Like I/análise , Hormônio do Crescimento/sangue , Adenoma/diagnóstico , Estudos Retrospectivos , Seguimentos , Resultado do Tratamento , Distribuição por Sexo , Colômbia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Gigantismo/diagnóstico , Mutação/genética
10.
Biol Lett ; 15(5): 20190175, 2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-31039728

RESUMO

Baleen whales (Mysticeti) are major ecosystem engineers, thanks to their enormous size and bulk filter feeding strategy. Their signature gigantism is thought to be a relatively recent phenomenon, resulting from a Plio-Pleistocene mode shift in their body size evolution. Here, we report the largest whale fossil ever described: an Early Pleistocene (1.5-1.25 Ma) blue whale from Italy with an estimated body length of up to 26 m. Macroevolutionary modelling taking into account this specimen, as well as additional material from the Miocene of Peru, reveals that the proposed mode shift occurred either somewhat earlier, or perhaps not at all. Large-sized mysticetes comparable to most extant species have existed since at least the Late Miocene, suggesting a long-term impact on global marine ecosystems.


Assuntos
Ecossistema , Gigantismo , Animais , Tamanho Corporal , Fósseis , Humanos , Itália
11.
Nat Rev Endocrinol ; 15(5): 299-311, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30842651

RESUMO

Overgrowth syndromes are a heterogeneous group of rare disorders characterized by generalized or segmental excessive growth commonly associated with additional features, such as visceromegaly, macrocephaly and a large range of various symptoms. These syndromes are caused by either genetic or epigenetic anomalies affecting factors involved in cell proliferation and/or the regulation of epigenetic markers. Some of these conditions are associated with neurological anomalies, such as cognitive impairment or autism. Overgrowth syndromes are frequently associated with an increased risk of cancer (embryonic tumours during infancy or carcinomas during adulthood), but with a highly variable prevalence. Given this risk, syndrome-specific tumour screening protocols have recently been established for some of these conditions. Certain specific clinical traits make it possible to discriminate between different syndromes and orient molecular explorations to determine which molecular tests to conduct, despite the syndromes having overlapping clinical features. Recent advances in molecular techniques using next-generation sequencing approaches have increased the number of patients with an identified molecular defect (especially patients with segmental overgrowth). This Review discusses the clinical and molecular diagnosis, tumour risk and recommendations for tumour screening for the most prevalent generalized and segmental overgrowth syndromes.


Assuntos
Neoplasias/epidemiologia , Neoplasias/genética , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/genética , Arritmias Cardíacas/patologia , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/epidemiologia , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Gigantismo/epidemiologia , Gigantismo/genética , Gigantismo/patologia , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/patologia , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Megalencefalia/epidemiologia , Megalencefalia/genética , Megalencefalia/patologia , Neoplasias/patologia , Gravidez , Fatores de Risco , Síndrome de Sotos/epidemiologia , Síndrome de Sotos/genética , Síndrome de Sotos/patologia , Síndrome
12.
Prog Mol Biol Transl Sci ; 161: 47-67, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30711029

RESUMO

X-linked acrogigantism (XLAG) is a recently described early-onset gigantism due to GPR101 duplication that induces growth hormone (GH) oversecretion. GPR101, which belongs to Family A rhodopsin-like family of G protein-coupled receptors, is predominantly expressed in hypothalamus and pituitary, suggesting that GPR101 might be important in regulating diverse functions such as energy balance and reproduction. Most mammalian GPR101s have extremely long third intracellular loops (ICL3); however, zebrafish GPR101 has a much shorter ICL3, but a longer C-terminus. GnRH-(1-5), a GnRH metabolite, can modulate the hypothalamus-pituitary-gonad axis and cancer cell migration via activating GPR101. GPR101 couples to both Gαs and Gαi proteins. GPR101 duplication has a causative role in XLAG, while GPR101 variants, especially c.924G>C (E308D), located at ICL3, are attributed to acromegaly. Some GPR101 mutations that are associated with a small proportion of pituitary tumors without GH oversecretion have also been identified recently. This chapter will summarize studies on GPR101, including its molecular cloning and tissue distribution, physiology, pharmacology, and pathophysiology.


Assuntos
Acromegalia/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Gigantismo/genética , Receptores Acoplados a Proteínas-G/genética , Sequência de Aminoácidos , Humanos , Modelos Biológicos , Mutação/genética , Receptores Acoplados a Proteínas-G/química
13.
Am J Med Genet A ; 179(2): 285-289, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30667571

RESUMO

We present a case of a Chinese child with X-linked Simpson-Golabi-Behmel syndrome (SGBS). To the best of our knowledge, this is the first report of 46,XY disorders of sex development (ambiguous genitalia, cryptorchidism, and uterus in the pelvis) in surviving SGBS patients. Other external anomalies included characteristic facial anomalies, overgrowth, macrocephaly, organomegaly, pectus excavatum, and cryptorchidism. It could be that the GPC3 gene mutation caused Leydig cell dysfunction in our patient. Disorders of sex development can be included as part of the clinical spectrum of SGBS.


Assuntos
Arritmias Cardíacas/fisiopatologia , Criptorquidismo/fisiopatologia , Transtornos do Desenvolvimento Sexual/fisiopatologia , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Gigantismo/fisiopatologia , Cardiopatias Congênitas/fisiopatologia , Deficiência Intelectual/fisiopatologia , Anormalidades Múltiplas/genética , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/genética , China/epidemiologia , Criptorquidismo/diagnóstico , Criptorquidismo/genética , Transtornos do Desenvolvimento Sexual/diagnóstico , Transtornos do Desenvolvimento Sexual/genética , Feminino , Genes Ligados ao Cromossomo X , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/genética , Gigantismo/diagnóstico , Gigantismo/genética , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Humanos , Lactente , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Masculino , Mutação/genética
14.
Front Neuroendocrinol ; 52: 113-143, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30448536

RESUMO

Individuals with acromegaloid physical appearance or tall stature may be referred to endocrinologists to exclude growth hormone (GH) excess. While some of these subjects could be healthy individuals with normal variants of growth or physical traits, others will have acromegaly or pituitary gigantism, which are, in general, straightforward diagnoses upon assessment of the GH/IGF-1 axis. However, some patients with physical features resembling acromegaly - usually affecting the face and extremities -, or gigantism - accelerated growth/tall stature - will have no abnormalities in the GH axis. This scenario is termed pseudoacromegaly, and its correct diagnosis can be challenging due to the rarity and variability of these conditions, as well as due to significant overlap in their characteristics. In this review we aim to provide a comprehensive overview of pseudoacromegaly conditions, highlighting their similarities and differences with acromegaly and pituitary gigantism, to aid physicians with the diagnosis of patients with pseudoacromegaly.


Assuntos
Acromegalia/diagnóstico , Transtornos Cromossômicos/diagnóstico , Diagnóstico Diferencial , Gigantismo/diagnóstico , Transtornos do Metabolismo de Glucose/diagnóstico , Hipotireoidismo/diagnóstico , Lipodistrofia/diagnóstico , Síndrome de Marfan/diagnóstico , Anormalidades Musculoesqueléticas/diagnóstico , Osteocondrodisplasias/diagnóstico , Acromegalia/metabolismo , Transtornos Cromossômicos/metabolismo , Gigantismo/metabolismo , Transtornos do Metabolismo de Glucose/metabolismo , Humanos , Lipodistrofia/metabolismo , Anormalidades Musculoesqueléticas/metabolismo
16.
Eur J Med Genet ; 62(4): 243-247, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30048822

RESUMO

GPC3 and GPC4 are the only two genes in which mutations are known to cause Simpson-Golabi-Behmel syndrome type 1 (SGBS1). The majority of SGBS1 patients have point mutations or deletions in GPC3. Only one SGBS1 family has been reported with duplication of both GPC3 and GPC4. Although clinical presentation of SGBS1 in affected males is well defined, the phenotype in female carriers is less clear. In total, six female carriers with clinical expression of SGBS1 have been reported to date. In this study, we provide description of two families with rare duplications in both GPC3 and GPC4. These imbalances resulted in SGBS1 in males, while female carriers with skewed X-inactivation exhibited significant features of SGBS1 including congenital heart defect, hernias, intellectual disability and coarse facial features. In family 2, a SGBS diagnosis was not considered in the father until after the diagnosis had been first considered and made in the affected daughter. We emphasize on the importance of testing at risk females and careful examination of those who are found to be carriers of SGBS1. We also discuss and provide supportive evidence for the role of skewed X-inactivation in clinical expression of SGBS1 in female carriers.


Assuntos
Arritmias Cardíacas/genética , Duplicação Gênica , Doenças Genéticas Ligadas ao Cromossomo X/genética , Gigantismo/genética , Glipicanas/genética , Cardiopatias Congênitas/genética , Heterozigoto , Deficiência Intelectual/genética , Inativação do Cromossomo X , Adulto , Arritmias Cardíacas/patologia , Criança , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Gigantismo/patologia , Cardiopatias Congênitas/patologia , Humanos , Deficiência Intelectual/patologia , Masculino , Linhagem
17.
J Stomatol Oral Maxillofac Surg ; 120(5): 483-488, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30553040

RESUMO

Simpson-Golabi-Behmel Syndrome (SGBS) is an X-linked overgrowth syndrome characterized by pre- and post-natal overgrowth, typical facial appearance and multiple visceral, skeletal, and neurological anomalies. There is only few information in the current literature, on clinical and particularly dentofacial findings due to recent identification of the syndrome and its clinical overlap with other overgrowth syndromes. The aim of this case report is to present dentofacial findings in a 16-year-old boy who had been diagnosed with SGBS. Following comprehensive clinical, radiographic and histopathological examinations, six pathologically distinct lesions including odontogenic keratocyst, ameloblastoma, lateral periodontal cyst, dentigerous cyst and mucous retention cyst in both mandible and maxilla were identified. The clinical report is followed by a discussion aimed to clarify unique features of this condition and how practitioners should consider similar cases.


Assuntos
Doenças Genéticas Ligadas ao Cromossomo X , Gigantismo , Cardiopatias Congênitas , Deficiência Intelectual , Adolescente , Arritmias Cardíacas , Humanos , Masculino
18.
Pediatr Dev Pathol ; 22(1): 70-74, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29652239

RESUMO

Simpson-Golabi-Behmel syndrome type I (SGBS, OMIM312870), caused by defects of the GPC3 and GPC4 genes on chromosome Xq26, is an X-linked recessive macrosomia/multiple congenital anomaly disorder characterized by somatic overgrowth, coarse facial features, variable congenital anomalies, increased tumor risk, and mild-to-moderate neurodevelopmental anomalies. We report the postmortem findings in 3 second-trimester male siblings with SGBS who displayed ambiguous genitalia (in all 3) and gonadal dysgenesis (ovotestis) (in 1), thus expanding the SGBS spectrum to include these disorders of sex development.


Assuntos
Anormalidades Múltiplas/diagnóstico , Arritmias Cardíacas/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Gigantismo/diagnóstico , Cardiopatias Congênitas/diagnóstico , Deficiência Intelectual/diagnóstico , Transtornos Ovotesticulares do Desenvolvimento Sexual/diagnóstico , Anormalidades Múltiplas/patologia , Arritmias Cardíacas/patologia , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Gigantismo/patologia , Cardiopatias Congênitas/patologia , Humanos , Deficiência Intelectual/patologia , Masculino , Transtornos Ovotesticulares do Desenvolvimento Sexual/patologia , Natimorto
19.
Am J Med Genet A ; 179(2): 322-328, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30592149

RESUMO

Simpson-Golabi-Behmel syndrome (SGBS) is a rare genetic condition and is inherited in an X-linked recessive manner. The disease is caused by a change in the nucleotide sequence of an X-linked gene encoding glypican 3, a protein belonging to the heparan-sulfate membrane proteoglycan family. SGBS case studies are almost entirely restricted to the pediatric population. Scarce literature describing SGBS course in adults may be due to both the high mortality of SGBS patients in childhood and low rate of SGBS diagnosis in adults. We present a case of a 39-year-old man with an initial diagnosis of acromegaly. Genetic tests revealed a hitherto unreported deletion in the GPC3 gene. SGBS manifestations in our patient included tall stature, dysmorphic features, and central nervous system (CNS) anatomical pathology. MRI of the head visualized abnormalities of median line structures, a feature consistent with SGBS: an unclosed craniopharyngeal canal, a sellar-suprasellar cyst, dysmorphic pituitary gland, and a cyst of the septum pellucidum. Moreover, cardiomyopathy complicated by life-threatening paroxysmal ventricular tachycardia was diagnosed. Although various cardiac anomalies are often found in SGBS, their pathogenesis is unclear and may be multifactorial. We believe that the presented case contributes to a better understanding of SGBS and may help clinicians in introducing prophylaxis and treatment for its comorbidities.


Assuntos
Acromegalia/genética , Arritmias Cardíacas/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Gigantismo/genética , Glipicanas/genética , Cardiopatias Congênitas/genética , Deficiência Intelectual/genética , Acromegalia/fisiopatologia , Adulto , Arritmias Cardíacas/fisiopatologia , Sistema Nervoso Central , Criança , Éxons , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Testes Genéticos , Gigantismo/fisiopatologia , Cardiopatias Congênitas/fisiopatologia , Humanos , Deficiência Intelectual/fisiopatologia , Masculino , Anormalidades Musculoesqueléticas , Mutação/genética , Linhagem , Fenótipo , Deleção de Sequência
20.
Artigo em Inglês | MEDLINE | ID: mdl-30537625

RESUMO

Breath analysis offers a non-invasive and rapid diagnostic method for detecting various volatile organic compounds that could be indicators for different diseases, particularly metabolic disorders including type 2 diabetes mellitus. The development of type 2 diabetes mellitus is closely linked to metabolic dysfunction of adipose tissue and adipocytes. However, the VOC profile of human adipocytes has not yet been investigated. Gas chromatography with mass spectrometric detection and head-space needle trap extraction (two-bed Carbopack X/Carboxen 1000 needle traps) were applied to profile VOCs produced and metabolised by human Simpson Golabi Behmel Syndrome adipocytes. In total, sixteen compounds were identified to be related to the metabolism of the cells. Four sulphur compounds (carbon disulphide, dimethyl sulphide, ethyl methyl sulphide and dimethyl disulphide), three heterocyclic compounds (2-ethylfuran, 2-methyl-5-(methyl-thio)-furan, and 2-pentylfuran), two ketones (acetone and 2-pentanone), two hydrocarbons (isoprene and n-heptane) and one ester (ethyl acetate) were produced, and four aldehydes (2-methyl-propanal, butanal, pentanal and hexanal) were found to be consumed by the cells of interest. This study presents the first profile of VOCs formed by human adipocytes, which may reflect the activity of the adipose tissue enzymes and provide evidence of their active role in metabolic regulation. Our data also suggest that a previously reported increase of isoprene and sulphur compounds in diabetic patients may be explained by their production by adipocytes. Moreover, the unique features of this profile, including a high emission of dimethyl sulphide and the production of furan-containing VOCs, increase our knowledge about metabolism in adipose tissue and provide diagnostic potential for future applications.


Assuntos
Adipócitos/metabolismo , Arritmias Cardíacas/metabolismo , Doenças Genéticas Ligadas ao Cromossomo X/metabolismo , Gigantismo/metabolismo , Cardiopatias Congênitas/metabolismo , Deficiência Intelectual/metabolismo , Compostos Orgânicos Voláteis/análise , Biomarcadores/análise , Biomarcadores/metabolismo , Células Cultivadas , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Compostos Orgânicos Voláteis/metabolismo
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