RESUMEN
Leri-Weill syndrome (LWS) is a skeletal dysplasia with mesomelic short stature, bilateral Madelung deformity (BMD) and SHOX (short stature homeobox-containing gene) haploinsufficiency. The effect of 24 months of recombinant human growth hormone (rhGH) therapy on the stature and BMD of two females with SHOX haploinsufficiency (demonstrated by fluorescence in situ hybridisation) and LWS was evaluated. Both patients demonstrated an increase in height standard deviation score (SDS) and height velocity SDS over the 24 months of therapy. Patient 1 demonstrated a relative increase in arm-span and upper segment measurements with rhGH while patient 2 demonstrated a relative increase in lower limb length. There was appropriate advancement of bone age, no adverse events and no significant deterioration in BMD. In this study, 24 months of rhGH was a safe and effective therapy for the disproportionate short stature of SHOX haploinsufficiency, with no clinical deterioration of BMD.
Asunto(s)
Estatura/efectos de los fármacos , Estatura/genética , Trastornos del Crecimiento/tratamiento farmacológico , Trastornos del Crecimiento/genética , Hormona del Crecimiento/uso terapéutico , Proteínas de Homeodominio/genética , Adolescente , Brazo/anatomía & histología , Brazo/crecimiento & desarrollo , Huesos/diagnóstico por imagen , Niño , Femenino , Mano/diagnóstico por imagen , Haplotipos , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Pierna/anatomía & histología , Pierna/crecimiento & desarrollo , Masculino , Fenotipo , Radiografía , Proteína de la Caja Homeótica de Baja EstaturaRESUMEN
This study was designed to determine the intrafamilial effect of SHOX haploinsufficiency on stature, by comparing the growth and phenotype of 26 SHOX haploinsufficient individuals with 45 relatives and population standards. It confirmed that SHOX haploinsufficiency leads to growth restriction from birth to final height. Compared to unaffected siblings, the SHOX haploinsufficient cohort was 2.14 SDS (3.8 cm) shorter at birth and 2.1 SDS shorter through childhood. At final height females were 2.4 SDS (14.4 cm) shorter and males 0.8 SDS (5.3 cm) shorter than normal siblings. The family height analysis suggests that the effect of SHOX haploinsufficiency on growth may have been previously underestimated at birth and overestimated in males at final height. SHOX haploinsufficiency leads to short arms in 92%, bilateral Madelung deformity in 73% and short stature in 54%. Females were more severely affected than males. We conclude that SHOX is a major growth gene and that mutations are associated with a broad range of phenotype.
Asunto(s)
Desarrollo Óseo/genética , Trastornos del Crecimiento/genética , Crecimiento/genética , Proteínas de Homeodominio/genética , Adolescente , Adulto , Determinación de la Edad por el Esqueleto , Anciano , Brazo/anatomía & histología , Brazo/crecimiento & desarrollo , Estatura/genética , Estatura/fisiología , Densidad Ósea/genética , Densidad Ósea/fisiología , Huesos/diagnóstico por imagen , Niño , Estudios de Cohortes , Femenino , Genotipo , Haplotipos , Humanos , Recién Nacido , Pierna/anatomía & histología , Pierna/crecimiento & desarrollo , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Proteína de la Caja Homeótica de Baja Estatura , SíndromeAsunto(s)
Síndrome Branquio Oto Renal/genética , Cromosomas Humanos Par 14/genética , Predisposición Genética a la Enfermedad/genética , Síndrome Branquio Oto Renal/patología , Mapeo Cromosómico , ADN/genética , Salud de la Familia , Femenino , Genoma Humano , Haplotipos/genética , Humanos , Escala de Lod , Masculino , Repeticiones de Microsatélite , LinajeAsunto(s)
Estatura/genética , Genes Homeobox/genética , Proteínas de Homeodominio/genética , Mutación/genética , Osteocondrodisplasias/genética , Estudios de Cohortes , Femenino , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/genética , Humanos , Masculino , Osteocondrodisplasias/epidemiología , Linaje , Prevalencia , Proteína de la Caja Homeótica de Baja Estatura , SíndromeRESUMEN
We tested the hypothesis that X-linked genes determining stature which are subject to skewed or non-random X-inactivation can account for discordance in height in monozygotic female twins. Height discordant female monozygotic adult twins (20 pairs) were identified from the Australian Twin Registry, employing the selection criteria of proven monozygosity and a measured height discordance of at least 5 cm. Differential X-inactivation was examined in genomic DNA extracted from peripheral lymphocytes by estimating differential methylation of alleles at the polymorphic CAG triplet repeat of the Androgen receptor gene (XAR). There were 17/20 MZ pairs heterozygous at this locus and informative for analysis. Of these, 10/17 both had random X-inactivation, 5/17 showed identical X-inactivation patterns of non random inactivation and 2/17 (12%) showed discordant X-inactivation. There was no relationship between inactivation patterns and self-report chorionicity. We conclude that non-random X-inactivation does not appear to be a major contributor to intra-pair height discordance in female MZ twins.
Asunto(s)
Estatura/genética , Compensación de Dosificación (Genética) , Ligamiento Genético/genética , Sistema de Registros , Gemelos Monocigóticos/genética , Adulto , Estudios de Cohortes , Desoxirribonucleasa HpaII , Femenino , Humanos , Reacción en Cadena de la Polimerasa , Factores Sexuales , Repeticiones de Trinucleótidos/genética , Estudios en Gemelos como AsuntoRESUMEN
Leri-Weill syndrome (LWS) is a dominant (pseudoautosomal) skeletal dysplasia with mesomelic short stature and bilateral Madelung deformity, due to dyschondrosteosis of the distal radius. It results from the loss of one copy of the Short Stature Homeobox Gene (SHOX) from the tip of the short arm of the X or Y chromosome. SHOX molecular testing enabled us to evaluate the histopathology of the radial physis in LWS patients with a documented SHOX abnormality. A widespread disorganisation of physeal anatomy was revealed with disruption of the normal parallel columnar arrangement of chondrocytes. Tandem stacking of maturing chondrocytes within columns was replaced by a side-by-side arrangement. The presence of hypertrophic osteoid with micro-enchondromata in the radial metaphysis suggests abnormal endochondral ossification. The Vickers' ligament was confirmed to blend with the triangular fibrocartilage complex (TFCC). This histopathological study demonstrates that the zone of dyschondrosteosis in LWS is characterised by marked disruption of normal physeal chondrocyte processes and that a generalised physeal abnormality is present.
Asunto(s)
Placa de Crecimiento/patología , Proteínas de Homeodominio/genética , Osteocondrodisplasias/patología , Osteocondrodisplasias/cirugía , Radio (Anatomía)/anomalías , Adolescente , Estatura , Niño , Aberraciones Cromosómicas , Femenino , Estudios de Seguimiento , Humanos , Mutación , Osteocondrodisplasias/genética , Radio (Anatomía)/cirugía , Rango del Movimiento Articular , Proteína de la Caja Homeótica de Baja Estatura , Resultado del Tratamiento , Articulación de la Muñeca/fisiopatologíaRESUMEN
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy (CADASIL) is a recently described cause of stroke or stroke-like episodes. It is caused by mutations in the Notch3 gene on chromosome 19p. We sought to demonstrate mutations of the Notch3 gene in Australian patients suspected of having CADASIL. Patients from several families were referred to the study. A diagnosis was determined clinically and by neuroimaging. Those suspected of having CADASIL had sequencing of exons 3 and 4 of the Notch3 gene. Eight patients, two of whom were siblings, were suspected of having CADASIL. Five patients (including the siblings) had mutations. Because of strong clustering of Notch3 mutations in CADASIL, this has potential as a reliable test for the disease in Australian patients.
Asunto(s)
Demencia por Múltiples Infartos/genética , Proteínas Proto-Oncogénicas/genética , Receptores de Superficie Celular , Anciano , Australia , Demencia por Múltiples Infartos/diagnóstico por imagen , Exones , Genotipo , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Mutación Puntual , Radiografía , Receptor Notch3 , Receptores NotchRESUMEN
BACKGROUND: There is a need for simple, rapid, and inexpensive methods for the detection of single-nucleotide polymorphisms. Our aim was to develop a single-tube ELISA-like PCR assay and evaluate it by detecting the common C282Y and H63D mutations found in the hemochromatosis gene (HFE) by use of clinical samples. METHODS: The method, termed solid-phase amplification (SPA), involves dual liquid- and solid-phase amplification of a target sequence by the use of two PCR primers, one of which is in two forms: the first is covalently immobilized to the wall of a microwell, and the second is free in solution. During allele-specific amplification, both the free and solid-phase amplicons are labeled by incorporation of digoxigenin (DIG)-dUTP. The amount of surface-bound amplicon is determined colorimetrically by the use of an alkaline phosphatase-anti-DIG-Fab conjugate and p-nitrophenyl phosphate. RESULTS: Two different amplicon-labeling methods were evaluated. Analysis of 173 clinical samples for the C282Y and H63D HFE point mutations with SPA revealed that only one sample was incorrectly diagnosed, apparently because of operator error, when compared with conventional restriction fragment length polymorphism assay results. CONCLUSIONS: The SPA assay has potential for medium-scale mutation detection, having the advantage of being manipulatively simple and immediately adaptable for use in clinical laboratories with existing ELISA instrumentation.
Asunto(s)
Antígenos HLA/genética , Hemocromatosis/genética , Antígenos de Histocompatibilidad Clase I/genética , Proteínas de la Membrana , Electroforesis en Gel de Agar , Proteína de la Hemocromatosis , Humanos , Mutación Missense , Mutación Puntual , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Sensibilidad y EspecificidadRESUMEN
We report on a patient with a severe premature calvarial synostosis and epidermal hyperplasia. The phenotype was consistent with that of a mild presentation of Beare-Stevenson syndrome but molecular analysis of the IgIII-transmembrane linker region and the transmembrane domain of the gene encoding the FGFR2 receptor, revealed wild-type sequence only. Subsequently, molecular analysis of the FGFR3 receptor gene identified a heterozygous P250R missense mutation in both the proposita and her mildly affected father. This communication extends the clinical spectrum of the FGFR3 P250R mutation to encompass epidermal hyperplasia and documents the phenomenon of activated FGFR receptors stimulating common downstream developmental pathways, resulting in overlapping clinical outcomes.
Asunto(s)
Craneosinostosis/genética , Proteínas Tirosina Quinasas , Receptores de Factores de Crecimiento de Fibroblastos/genética , Piel/patología , Sustitución de Aminoácidos , Craneosinostosis/patología , ADN/química , ADN/genética , Análisis Mutacional de ADN , Femenino , Humanos , Hiperplasia , Lactante , Mutación Missense , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos , Enfermedades de la Piel/genética , Enfermedades de la Piel/patologíaAsunto(s)
Acidosis Láctica/genética , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/genética , Terapia Antirretroviral Altamente Activa/efectos adversos , ADN Mitocondrial/genética , Eliminación de Secuencia , Acidosis Láctica/inducido químicamente , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Humanos , Lamivudine/uso terapéutico , Masculino , Persona de Mediana Edad , Saquinavir/uso terapéutico , Estavudina/uso terapéuticoRESUMEN
We report on a patient with the skeletal findings of Jackson-Weiss syndrome, who manifests only mild craniofacial anomalies. Molecular analysis of her fibroblast growth factor receptor 1 gene (FGFR1) identified a heterozygous P252R missense mutation, previously only reported with FGFR1-Pfeiffer syndrome like manifestations. Mutations in the immunoglobulin-like, II-III (IgII-III) linker region of FGFR1 and FGFR3 molecules may present as a skeletal dysplasia affecting the appendicular skeleton including, brachydactyly, short broad middle phalanges, phalangeal epiphyseal coning and broad halluces. This communication is a further example of the phenomenon of an activated FGFR molecule resulting in overlapping manifestations in FGFR syndromes.
Asunto(s)
Anomalías Múltiples/genética , Mutación Missense , Proteínas Tirosina Quinasas Receptoras/genética , Receptores de Factores de Crecimiento de Fibroblastos/genética , Anomalías Múltiples/diagnóstico por imagen , Secuencia de Bases , Niño , Cartilla de ADN , Facies , Femenino , Humanos , Osteocondrodisplasias/diagnóstico por imagen , Osteocondrodisplasias/genética , Radiografía , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos , SíndromeRESUMEN
PURPOSE: To determine whether prostatic cells were normally present in ejaculate and if the sensitivity and specificity of the detection of malignant prostate cells in ejaculate and urethral washings from men with suspected prostate cancer could be improved using the more sensitive molecular technique of reverse transcriptase-polymerase chain reaction (RT-PCR). MATERIALS AND METHODS: RT-PCR for prostate-specific antigen (PSA), prostate-specific membrane antigen (PSM) and Apoliprotein D (3 putative prostate-specific and/or cancer-specific markers) was performed on RNA extracts of ejaculate (80) and urethral washings (52) from 77 men with suspected prostate cancer and 12 young controls (<30 years of age) and urines from 5 men who had radical prostatectomies and 10 women. RESULTS: PSA, PSM and Apolipoprotein D expression was detected in ejaculates and urethral washings from both patient and control groups. No differences were observed in the results obtained for 58 men with suspected or 19 men with confirmed prostate cancer or the 18 vasectomized men within the patient group. Urines from the 5 men who had radical prostatectomies and 10 women were all negative for PSA, but PSM was detected in 2 female urines and in 3 radical prostatectomy samples. As few as 10 LNCaP prostate tumor cells could be detected by PSA RT-PCR when added to female urine. CONCLUSION: We have established a sensitive method of detecting prostatic cells in ejaculate and urethral washings and shown that PSA RT-PCR is a reliable indicator of prostate cells in these samples. However, RT-PCR for PSA, PSM and Apoliprotein D were not useful for discriminating malignant from non-malignant prostate cells.
Asunto(s)
Antígenos de Superficie , Eyaculación , Neoplasias de la Próstata/patología , Orina/citología , Adulto , Antígenos de Neoplasias/análisis , Apolipoproteínas/análisis , Apolipoproteínas D , Biomarcadores/análisis , Carboxipeptidasas/análisis , Femenino , Glutamato Carboxipeptidasa II , Humanos , Masculino , Antígeno Prostático Específico/análisis , Neoplasias de la Próstata/química , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Irrigación Terapéutica , Uretra , Orina/químicaRESUMEN
The RET proto-oncogene encodes a receptor tyrosine kinase activated by the binding of factors from the glial cell line-derived neurotrophic factor (GDNF) family to receptor-alpha components such as GDNF family receptor alpha-1 (GFR alpha-1). Mutations within the sequence of the RET proto-oncogene are associated with multiple endocrine neoplasia type 2 (MEN 2), an inherited tumor syndrome characterized by the development of medullary thyroid carcinoma (MTC) and other neuroendocrine tumors. Despite Northern analysis showing that RET is expressed in the majority of MTCs, the factors regulating this expression are poorly understood. To address this issue we examined RET expression in response to glucocorticoids in the TT cell line, derived from a metastatic MTC. The synthetic glucocorticoid dexamethasone was found to reduce RET expression at both mRNA and protein levels. This effect was dose responsive and maximal at 24 h. The reduction in RET mRNA was shown to be specific to glucocorticoids and was also seen in a primary MTC culture. Nuclear run-on studies revealed the reduction in steady-state RNA to be due to a decrease in RET mRNA transcription and the effect was shown to be independent of new protein synthesis or RNA stability. Dexamethasone was also found to exert an inhibitory effect upon cell growth, suggesting a potential use for glucocorticoids in the treatment of medullary carcinoma and MEN 2.
Asunto(s)
Proteínas de Drosophila , Glucocorticoides/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Carcinoma Medular/genética , Carcinoma Medular/metabolismo , División Celular , Dexametasona/metabolismo , Dexametasona/farmacología , Relación Dosis-Respuesta a Droga , Regulación Neoplásica de la Expresión Génica , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial , Glucocorticoides/farmacología , Humanos , Pregnenodionas/farmacología , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/efectos de los fármacos , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-ret , Proteínas Tirosina Quinasas Receptoras/efectos de los fármacos , Proteínas Tirosina Quinasas Receptoras/genética , Esteroides/metabolismo , Esteroides/farmacología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Transcripción Genética , Células Tumorales CultivadasRESUMEN
Specific germline mutations in the RET proto-oncogene predispose to the familial cancer syndromes: multiple endocrine neoplasia (MEN) types 2A and 2B, and familial medullary thyroid carcinoma. Expression of the RET receptor tyrosine kinase is tightly restricted to tumours of neural crest origin, such as neuroblastoma, and neuroblastoma has been observed in RET transgenic mice. Neuroblastoma tumour cell lines transfected with the MEN2A RET gene exhibit spontaneous neuritic differentiation, whereas MEN2B-type RET transfectants demonstrate altered cell adhesion and enhanced metastatic potential. In this study, the authors examined genomic DNA from 26 primary neuroblastoma tumours for MEN2A and MEN2B RET mutations, using restriction enzyme digestion of polymerase chain reaction products as an alternative to direct sequencing. Examination of RET exons 10 (codons 611, 618, 620), 11 (codons 632, 633, 634) and 16 (codon 918) in all 26 tumours revealed no RET mutations. Taken together these data suggest that abnormalities of the RET signalling pathway, rather than oncogenic, MEN2-type RET activation by mutation, may play a role in neuroblastoma tumorigenesis.
Asunto(s)
Proteínas de Drosophila , Neoplasia Endocrina Múltiple Tipo 2a/genética , Neoplasia Endocrina Múltiple Tipo 2b/genética , Mutación , Neuroblastoma/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Tirosina Quinasas Receptoras/genética , ADN de Neoplasias/análisis , Humanos , Neoplasia Endocrina Múltiple Tipo 2a/enzimología , Neoplasia Endocrina Múltiple Tipo 2b/enzimología , Neuroblastoma/química , Neuroblastoma/enzimología , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-ret , Células Tumorales CultivadasRESUMEN
We have estimated how much of the total genetic predisposition to SLE may be attributable to genes outside the HLA region by comparing figures for concordance of SLE in monozygotic twins with those for concordance in HLA identical siblings in Australia. None of six dizygotic co-twins of white Australian SLE probands was concordant for SLE. One of four (25%) monozygotic co-twins of white Australian SLE probands was concordant for SLE which when added to previously published figures for Caucasoid populations gives an overall concordance rate for SLE in monozygotic twins of 25%. None of 18 HLA identical, same sex siblings of SLE probands, had definite SLE by the study criteria (i.e. less than 6%). The comparison of these figures shows that most of the genetic predisposition to SLE is attributable to genes outside the HLA region.
Asunto(s)
Enfermedades en Gemelos/diagnóstico , Enfermedades en Gemelos/genética , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/genética , Adolescente , Adulto , Anciano , Australia/epidemiología , Niño , Enfermedades en Gemelos/epidemiología , Femenino , Haplotipos , Humanos , Lupus Eritematoso Sistémico/epidemiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Gemelos Dicigóticos , Gemelos MonocigóticosRESUMEN
OBJECTIVE: To examine the in vitro expression of E-selectin, P-selectin, intercellular adhesion molecule 1 (ICAM-1), ICAM-2, vascular cell adhesion molecule 1 (VCAM-1), and platelet-endothelial cell adhesion molecule 1 (PECAM-1) by synovial microvascular endothelial cells (SMEC) in comparison with microvascular neonatal foreskin endothelial cells (FSE) and macrovas- cular human umbilical vein endothelial cells (HUVE). METHODS: Cultured endothelial cells were treated for 4 hours with medium alone or tumor necrosis factor alpha (TNF alpha). The expression of endothelial adhesion molecules was evaluated by flow cytometry, cell enzyme-linked immunosorbent assay, and Northern blot analysis. RESULTS: SMEC continuously expressed E-selectin under basal culture conditions, whereas FSE and HUVE did not. TNF alpha treatment of rheumatoid arthritis (RA) SMEC resulted in sustained peak expression of E- selectin for up to 24 hours, which subsequently declined but remained elevated even at 72 hours. In contrast, peak E-selectin expression in FSE and HUVE occurred between 4 hours and 16 hours after TNF alpha treatment and then declined to near basal levels by 24-48 hours. SMEC expressed significantly higher levels of ICAM-1 compared with HUVE under basal culture conditions. There was no difference between SMEC, FSE, and HUVE in the expression of P-selectin, VCAM-1, ICAM-2, or PECAM-1. Northern blot analysis demonstrated that the levels of E-selectin expression by TNF alpha stimulated endothelial cells correlated with their respective messenger RNA levels. CONCLUSION: Regulation of E-selectin and ICAM-1 expression in RA synovial endothelium is different from that in neonatal foreskin and human umbilical vein endothelium. The augmented expression of adhesion molecules in RA synovial endothelium may facilitate the recruitment of leukocytes to this site.
Asunto(s)
Moléculas de Adhesión Celular/genética , Endotelio Vascular/fisiología , Membrana Sinovial/irrigación sanguínea , Aglutininas , Antígenos CD/genética , Antígenos de Diferenciación Mielomonocítica/genética , Artritis Reumatoide/patología , Northern Blotting , Moléculas de Adhesión Celular/inmunología , Células Cultivadas/fisiología , Selectina E/genética , Humanos , Molécula 1 de Adhesión Intercelular/genética , Masculino , Microcirculación , Microesferas , Osteoartritis/patología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta , ARN Mensajero/análisis , Piel/citología , Membrana Sinovial/citología , Membrana Sinovial/fisiología , Molécula 1 de Adhesión Celular Vascular/genéticaRESUMEN
OBJECTIVE: The pentagastrin stimulation test is the traditional test used for the identification of asymptomatic individuals in multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC). The identification of mutations in the RET proto-oncogene segregating with the disease phenotype in MEN 2A and FMTC families has made it possible to re-examine the validity of using this test for the identification of affected family members. DESIGN: Sequential and single pentagastrin stimulation test data were collected following the identification of RET mutation positive and RET mutation negative members of families with MEN 2A or FMTC. PATIENTS: RET mutations were identified in 16 Australian and New Zealand MEN 2A or FMTC families. An analysis of 39 individuals from these families was included in this study. Thirty-two individuals (14 males, 18 females) had previously been determined as RET mutation negative. Seven individuals (6 males, 1 female) had previously been determined as RET mutation positive. Two RET mutation negative males had thyroidectomy based on prior pentagastrin test results. MEASUREMENTS: Serum calcitonin levels in response to stimulation with pentagastrin were measured at 0, 1, 2, 5 and 10 minutes post injection. Mutation analysis of the RET proto-oncogene was performed in all individuals. In two RET mutation negative individuals from two MEN 2A families, thyroidectomy was performed and C-cells were quantitated in order to determine the diagnosis of C-cell hyperplasia. RESULTS: There was a statistically significant difference (P < 0.013) between RET mutation negative male and female mean peak calcitonin responses of 282 +/- 236 and 96 +/- 62 (mean +/- SD) ng/l respectively. False positive responses to pentagastrin stimulation were identified in seven individuals who were RET mutation negative in two of the 16 families. Histologic examination of the thyroid glands in the two RET mutation negative individuals who had thyroidectomy demonstrated C-cell hyperplasia in one but not in the other. CONCLUSIONS: There is considerable overlap between pentagastrin test results in individuals who are RET mutation positive and those who are RET mutation negative. These results indicate a need for routine performance of RET proto-oncogene analysis on all individuals at risk of developing MEN 2A or FMTC and a coupling of pentagastrin test results and RET proto-oncogene analysis in the decision to proceed with thyroidectomy.
Asunto(s)
Proteínas de Drosophila , Neoplasia Endocrina Múltiple Tipo 2a/diagnóstico , Pentagastrina , Adolescente , Adulto , Calcitonina/sangre , Carcinoma Medular/diagnóstico , Niño , Análisis Mutacional de ADN , Reacciones Falso Positivas , Femenino , Humanos , Hiperplasia , Masculino , Neoplasia Endocrina Múltiple Tipo 2a/genética , Linaje , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-ret , Proteínas Tirosina Quinasas Receptoras/genética , Glándula Tiroides/patología , Neoplasias de la Tiroides/diagnósticoRESUMEN
The frequency of the uncommon allele (TNF2) of a polymorphism in the promoter region of the tumour necrosis factor alpha (TNF alpha) gene in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) was found to be 3 times that of the normal anglo-saxon population. In SLE patients, this allele was strongly associated with HLA-DR3 expression and was also more frequent in patients who did not have malar rash. Functional studies of normal monocyte cytokine production in vitro showed that this genotype was associated with increased IL-1 alpha protein production but there were no differences in the production of TNF alpha protein.