RESUMEN

Single photon emission computerized tomography (SPECT) studies were performed on 34 manifest Huntington's disease (HD) patients at various stages of clinical pathology ranging from early chorea to late dystonia with or without signs of dementia and 12 pre-symptomatic patients with abnormal terminal CAG expansions. Thirty HD patients with obvious clinical signs and seven pre-symptomatic patients without signs or symptoms of HD displayed selective caudate hypoperfusion by direct visual inspection. Such qualitative, selective striatal hypoperfusion patterns can be indicative of early and persistent metabolic changes in striatal neuropathology. SPECT studies can be useful in documenting early pre-clinical changes in patients with abnormal terminal CAG expansions and in confirming the presence of caudate pathology in patients with clinical signs of HD.

Asunto(s)

Enfermedad de Huntington/diagnóstico por imagen , Degeneración Nerviosa/diagnóstico por imagen , Adulto , Anciano , ADN/genética , Femenino , Humanos , Enfermedad de Huntington/genética , Masculino , Persona de Mediana Edad , Degeneración Nerviosa/genética , Radiofármacos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tomografía Computarizada de Emisión de Fotón Único

RESUMEN

Wnt-4, a member of the Wnt family of locally acting secreted growth factors, is the first signaling molecule shown to influence the sex-determination cascade. In mice, a targeted deletion of Wnt-4 causes the masculinization of XX pups. Therefore, WNT-4, the human homologue of murine Wnt-4, is a strong candidate gene for sex-reversal phenotypes in humans. In this article, we show that, in testicular Sertoli and Leydig cells, Wnt-4 up-regulates Dax1, a gene known to antagonize the testis-determining factor, Sry. Furthermore, we elucidate a possible mechanism for human XY sex reversal associated with a 1p31-p35 duplication including WNT-4. Overexpression of WNT-4 leads to up-regulation of DAX1, which results in an XY female phenotype. Thus, WNT-4, a novel sex-determining gene, and DAX1 play a concerted role in both the control of female development and the prevention of testes formation. These observations suggest that mammalian sex determination is sensitive to dosage, at multiple steps in its pathway.

Asunto(s)

Proteínas de Unión al ADN/metabolismo , Trastornos del Desarrollo Sexual , Proteínas Proto-Oncogénicas/metabolismo , Receptores de Ácido Retinoico/metabolismo , Proteínas Represoras , Procesos de Determinación del Sexo , Transducción de Señal , Factores de Transcripción/metabolismo , Regulación hacia Arriba , Secuencia de Aminoácidos , Animales , Línea Celular , Cromosomas Humanos Par 1/genética , Receptor Nuclear Huérfano DAX-1 , Proteínas de Unión al ADN/biosíntesis , Proteínas de Unión al ADN/genética , Femenino , Fibroblastos , Dosificación de Gen , Genes Duplicados/genética , Humanos , Hibridación Fluorescente in Situ , Células Intersticiales del Testículo/metabolismo , Masculino , Ratones , Datos de Secuencia Molecular , Proteínas Proto-Oncogénicas/biosíntesis , Proteínas Proto-Oncogénicas/genética , Receptores de Ácido Retinoico/biosíntesis , Receptores de Ácido Retinoico/genética , Alineación de Secuencia , Células de Sertoli/metabolismo , Factores de Transcripción/biosíntesis , Factores de Transcripción/genética , Transfección , Proteínas Wnt , Proteína Wnt4

RESUMEN

Twenty-six laboratories used X and Y chromosome probes and the same procedures to process and examine 15,600 metaphases and 49,400 interphases from Phaseolus vulgaris-leucoagglutinin (PHA)-stimulated lymphocytes. In Part I, each laboratory scored 50 metaphases and 200 interphases from a normal male and a normal female from its own practice. In Part II, each laboratory scored 50 metaphases and 200 interphases on slides prepared by a central laboratory from a normal male and a normal female and three mixtures of cells from the male and female. In Part III, each laboratory scored 50 metaphases (in samples of 5, 10, 15, and 20) and 100 interphases (in samples of 5, 10, 15, 20, and 50) on new, coded slides of the same specimens used in Part II. Metaphases from male specimens were scored as 98-99% XY with no XX cells, and 97-98% of interphases were scored as XY with 0.04% XX cells. Metaphases from female specimens were scored as 96-97% XX with 0.03% XY cells, and 94-96% of interphases were scored as XX with 0.05% XY cells. Considering the data as a model for any probe used with fluorescence in situ hybridization (FISH), a statistical approach assessing the impact of analytical sensitivity on the numbers of observations required to assay for potential mosaicisms and chimerisms is discussed. The workload associated with processing slides and scoring 50 metaphases and 200 interphases using FISH averaged 27.1 and 28.6 minutes, respectively. This study indicates that multiple laboratories can test/develop guidelines for the rapid, efficacious, and cost-effective integration of FISH into clinical service.

Asunto(s)

Sondas de ADN , Hibridación Fluorescente in Situ/métodos , Interfase , Cromosoma X , Cromosoma Y , Citogenética/normas , Femenino , Humanos , Hibridación Fluorescente in Situ/instrumentación , Laboratorios/normas , Activación de Linfocitos , Linfocitos/citología , Masculino , Metafase , Fitohemaglutininas , Control de Calidad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Carga de Trabajo

Asunto(s)

Líquido Amniótico/citología , Aneuploidia , Enfermedades Fetales/genética , División Celular , Células Cultivadas , Femenino , Enfermedades Fetales/patología , Edad Gestacional , Humanos , Embarazo , Diagnóstico Prenatal

Asunto(s)

Deleción Cromosómica , Dermatosis Facial/complicaciones , Microftalmía/complicaciones , Cromosoma X , Anomalías Múltiples/patología , Oído Externo/anomalías , Huesos Faciales/anomalías , Dermatosis Facial/patología , Femenino , Humanos , Lactante , Recién Nacido , Microftalmía/patología , Síndrome

Asunto(s)

Anomalías Múltiples/genética , Microftalmía/genética , Anomalías Cutáneas , Translocación Genética , Agenesia del Cuerpo Calloso , Opacidad de la Córnea/congénito , Opacidad de la Córnea/genética , Femenino , Humanos , Recién Nacido , Síndrome , Cromosoma X

RESUMEN

The incidence of congenital syphilis is on the rise. Penicillin continues to be the drug of choice for it during pregnancy. A penicillin-allergic woman with primary stage syphilis who was treated initially with erythromycin presented with fever and nonimmune fetal hydrops secondary to an intrauterine syphilitic infection. Following desensitization and penicillin therapy the fetal hydrops disappeared, the pregnancy continued to term, and the patient delivered a small-for-gestational-age but other-wise normal infant who continued to do well up to 1 year of age.

Asunto(s)

Hipersensibilidad a las Drogas/etiología , Eritromicina/uso terapéutico , Hidropesía Fetal/etiología , Penicilinas/uso terapéutico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Sífilis/tratamiento farmacológico , Ultrasonografía Prenatal , Adulto , Desensibilización Inmunológica , Hipersensibilidad a las Drogas/tratamiento farmacológico , Femenino , Humanos , Hidropesía Fetal/diagnóstico por imagen , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Masculino , Embarazo

RESUMEN

Advances in medical genetics are providing a major clinical challenge to practitioners seeing patients concerned about their risk of developing either inherited disease or susceptibility to acquired disease. Popular information can easily exceed our professional ability to provide services to well-read patients who want answers with scientific certainty. The challenge also involves ethical questions regarding confidentiality and the way that results are disclosed. More often than not, the test itself becomes the focus of psychosocial expectations for the future and lifestyle of the patient and family. The behavioral consequences of disclosure of test results need to be anticipated by the caregiver to avoid adverse psychological outcomes.

Asunto(s)

ADN/análisis , Asesoramiento Genético , Tamización de Portadores Genéticos , Humanos , Enfermedad de Huntington/genética , Enfermedad de Huntington/psicología , Estilo de Vida

Asunto(s)

Mosaicismo , Fenotipo , Diagnóstico Prenatal , Aberraciones Cromosómicas Sexuales/diagnóstico , Cromosoma X , Adulto , Femenino , Humanos , Masculino , Embarazo

Asunto(s)

Anomalías Múltiples/diagnóstico , Cara/anomalías , Peroné/anomalías , Humanos , Riñón/anomalías , Síndrome , Cúbito/anomalías

RESUMEN

This paper demonstrates that the outcome of amniocenteses performed between the 9th and the 14th weeks is similar to that of amniocenteses performed between the 15th and 20th weeks. We have performed and prospectively followed 615 amniocenteses between the 9th and 16th weeks of gestation. The outcome, risks, and complications are similar to those of amniocenteses at the usual time (after 15 weeks) and to the other groups of early amniocentesis (before 15 weeks). Early amniocentesis differs from amniocentesis at the usual time in that it carries higher rates of fetal losses and of amniotic fluid leakage, more confined cytogenetic abnormalities, and an increased number of patients who have the procedure postponed. Two cultures (0.32%) failed to produce results, 595 (96.7%) samples were obtained at the first tapping, 20 (3.3%) at the second attempt. alpha-Fetoprotein levels reach their maximum at 13 weeks. Amniocenteses between 15 and 16 weeks (293, or 47%) constitute the control group, those between 9 and 14 weeks (322) the experimental group. Early amniocentesis appears to be a safe early genetic prenatal diagnosis technique, an alternative to chorionic villi sampling.

Asunto(s)

Amniocentesis/estadística & datos numéricos , Resultado del Embarazo/epidemiología , Riesgo , Amniocentesis/efectos adversos , Líquido Amniótico/análisis , Muestra de la Vellosidad Coriónica/efectos adversos , Femenino , Muerte Fetal/epidemiología , Humanos , Embarazo , Primer Trimestre del Embarazo , Segundo Trimestre del Embarazo , Diagnóstico Prenatal/estadística & datos numéricos , Estudios Prospectivos

RESUMEN

This paper presents the ultrasonographic analysis of the growth of two groups of human fetuses, one longitudinal and the other cross-sectional. Measurements of all the long bones were taken, as well as measurements of the following diameters: Biparietal, occipitofrontal, thoracic and abdominal anterior/posterior and transverse, spinal canal width, arm, forearm, thigh and leg transverse. The bladder and the stomach were also measured. The pregnancies analyzed covered the period between the 8th and 38th week of gestation. Centiles (3rd-97th) were calculated for each structure and week. All pregnancies known or suspected to be abnormal were removed from the study. The values obtained were tested in 102 pregnancies (test group); the expected values (from the graphs) did not deviate from the values obtained from this group of fetuses, demonstrating the reliability of the values presented in these graphs. All structures measured showed linear growth. There was no significant difference between the longitudinal and cross-sectional groups.

Asunto(s)

Feto/anatomía & histología , Ultrasonografía , Adolescente , Adulto , Huesos/anatomía & histología , Huesos/embriología , Estudios Transversales , Femenino , Retardo del Crecimiento Fetal/diagnóstico , Edad Gestacional , Humanos , Estudios Longitudinales , Embarazo , Valores de Referencia

Asunto(s)

Anomalías Congénitas/genética , Enfermedades Genéticas Congénitas/genética , Fenotipo , Diagnóstico Prenatal , Femenino , Humanos , Embarazo , Riesgo , Ultrasonografía

RESUMEN

The determination of acetylcholinesterase (AChE) has been shown to be as specific as alphafetoprotein (AFP) for the prenatal detection of open neural tube defects although AFP remains the method of choice. This paper describes a semi-automated technique for the analysis of acetylcholinesterase in amniotic fluid that: A) reduces the cost of the procedure; B) allows for a larger number of samples to be run at a time; and C) provides for more accurate and reproducible procedures and results. Six fetuses with neural tube defects (2 with gastroschisis and 3 where one twin was dead) were detected and found to have elevated AChE, TChE and 2 bands by electrophoresis. Quality control procedures using both pure enzyme and amniotic fluid with low and high levels of the enzyme are described. The analysis of 340 amniotic fluids of normal pregnancies indicates that the normal value for AChE is 5.17 +/- 2.63 mU/ml (97% confidence interval for the mean 4.84-5.49 mU/ml. A group of 27 abnormal pregnancies provides evidence that fetal vomiting and regurgitation, fetal demise, multiple cysts syndrome, idiopathic IUGR, arthrogryposis multiplex, hydrocephaly (stenosis of aqueductus), trisomy 21, trisomy 18, hydronephrosis, pyloric stenosis, heart malformation, ectopia cordis and multiple gestation produce elevated levels of pseudocholinesterase (PChE) in amniotic fluid. The use of pseudocholinesterase levels in amniotic fluid for prenatal diagnosis is proposed and discussed in view of its elevated levels in abnormal pregnancies where AChE is normal. The normal values for PChE are 23.86 mU/ml (mean) and 5.83 for standard deviation. Electrophoretic analysis was performed on all samples with values higher than one standard deviation above the mean.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

Acetilcolinesterasa/análisis , Líquido Amniótico/enzimología , Butirilcolinesterasa/análisis , Colinesterasas/análisis , Anomalías Congénitas/diagnóstico , Defectos del Tubo Neural/diagnóstico , Diagnóstico Prenatal/instrumentación , Anomalías Congénitas/enzimología , Enfermedades en Gemelos , Femenino , Feto/enzimología , Humanos , Defectos del Tubo Neural/enzimología , Embarazo , Diagnóstico Prenatal/economía , Estenosis Pilórica/diagnóstico , Estenosis Pilórica/enzimología , alfa-Fetoproteínas/análisis

RESUMEN

The results of the ultrasonographic determination of fetal gender in utero in 722 fetuses (13-35 weeks' gestation) are described, demonstrating that fetal genitalia can be seen in 60.5 per cent of those examined before the eighteenth week, and in 100 per cent of those examined twice or once after 20 weeks of gestation. All errors (3.04 per cent) of gender assignment occurred before the twenty-fourth week. When the fetus was examined for the first time at 17 weeks, the genitalia were visualized and correctly diagnosed in 282 males and 155 females; nine males and 13 females were incorrectly diagnosed. Ultrasonographic determination of fetal gender in utero is an integral part of the prenatal diagnosis of sex maldefinition, testicular feminization, and campomelic dysplasia. It has proved to be a reliable marker in determining whether each sac has been sampled in multiple pregnancies (when each fetus is in a different sac) if ultrasonographically assigned sex per twin corresponds to its karyotype. The determination of fetal gender in utero by ultrasonography allows for gender selection; some of its ethical implications are considered.

Asunto(s)

Feto/anatomía & histología , Genitales Femeninos/embriología , Genitales Masculinos/embriología , Ultrasonografía , Errores Diagnósticos , Ética Médica , Femenino , Edad Gestacional , Humanos , Masculino , Embarazo , Diagnóstico Prenatal , Aberraciones Cromosómicas Sexuales/diagnóstico , Análisis para Determinación del Sexo

RESUMEN

This paper describes two fetuses with thanatophoric dysplasia (TD) diagnosed in utero by ultrasonography. The fetuses were found to have severely short (less than 3rd centile), mildly bowed bones in one of them at 20 weeks and straight bones in the other at 34 weeks; bell-shaped chest; abnormal ribs (broadened and flattened at their ends); severe lung hypoplasia; hypoplastic, round-shaped vertebral bodies with hypoplastic arches; abnormally small pelvic bones, phalanges, metacarpals, and metatarsals. There was also an incipient "cloverleaf" skull deformity produced by fused posterior sagittal and lambdoidal sutures in the 20-week fetus and a definitive cloverleaf skull with communicating hydrocephaly in the 34-week fetus. The autopsies did not show any other abnormality. By xeroradiography after delivery, marked abnormalities of the endochondral and perichondral bone structures could be demonstrated in the 20-week fetus but not in the 34-week fetus. They appear to constitute two different conditions. These cases are good examples of the possibilities brought by ultrasound to the analysis of the fetal phenotype in utero.

Asunto(s)

Osteocondrodisplasias/diagnóstico , Displasia Tanatofórica/diagnóstico , Humanos , Fenotipo , Diagnóstico Prenatal , Radiografía , Displasia Tanatofórica/diagnóstico por imagen , Displasia Tanatofórica/embriología , Ultrasonido

RESUMEN

We examined 10 fetuses with nuchal cysts and compared the findings with 32 cases from the literature. Based on their characteristics, we propose that nuchal cysts are signs of four causally and pathogenetically different entities: cystic nuchal blebs present in otherwise normal fetuses as a postmortem change; 45,X fetuses who have a particular appearance and multiple congenital malformations; an apparently autosomal recessive syndrome of multiple cysts (that extend into deep muscular planes), generalized edema, cleft palate, peculiar skeletal characteristics, acutely angulated ribs (producing a bell-shaped rib cage), and shortened long bones; and in fetuses with syndromes that are inherited (multiple pterygium, Roberts) and chromosomal (trisomy 13, trisomy 21) as an unspecific sign representing both primary and secondary lesions.

Asunto(s)

Quistes/diagnóstico , Enfermedades Fetales/diagnóstico , Genes Recesivos , Cuello , Diagnóstico Prenatal , Anomalías Múltiples/patología , Quistes/genética , Quistes/patología , Síndrome de Down/patología , Femenino , Enfermedades Fetales/patología , Humanos , Recién Nacido , Masculino , Embarazo , Síndrome , Síndrome de Turner/patología

Asunto(s)

Anomalías Congénitas/diagnóstico , Osteocondrodisplasias/diagnóstico , Fenotipo , Diagnóstico Prenatal/métodos , Ultrasonografía , Femenino , Humanos , Embarazo

RESUMEN

We describe two sibs affected with Jeune syndrome. The first was diagnosed after birth and the second was diagnosed prenatally using ultrasonography. The detected abnormalities were confirmed by X-ray and autopsy following pregnancy termination. This observation indicates the possibility of prenatal diagnosis of the condition.

Asunto(s)

Asfixia Neonatal/complicaciones , Genes Recesivos , Osteocondrodisplasias/diagnóstico , Diagnóstico Prenatal , Displasia Tanatofórica/diagnóstico , Tórax/anomalías , Ultrasonografía , Adulto , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Displasia Tanatofórica/genética

RESUMEN

A fetus with Weyers oligodactyly was studied after a previous sibling had been born with that condition. Prenatal diagnosis was undertaken using ultrasound to visualize the long bones, which were found to be severely affected by the condition at 19 weeks of gestation. Most notable were the ulnae and fibulae, which were very short; the fetus had bilateral hydronephrosis.

Asunto(s)

Peroné/anomalías , Dedos/anomalías , Genes Recesivos , Hidronefrosis/genética , Diagnóstico Prenatal , Dedos del Pie/anomalías , Cúbito/anomalías , Ultrasonografía , Adulto , Femenino , Humanos , Hidronefrosis/diagnóstico , Masculino , Embarazo , Síndrome