ABSTRACT
BACKGROUND: Discovery of cell-free fetal DNA (cffDNA) in maternal blood in 1997 by Lo et al. has opened the possibility of a noninvasive prenatal test (NIPT). Currently, it is employed in the analysis of aneuploidies and fetal sex determination. Massive parallel sequencing (MPS) detects the origin of each amplified sequence, and analyses over-representation of sequences or any decrease in the fetal chromosomes in maternal plasma. This technique has been validated and allows assessment of trisomies 13, 18 and 21, obtaining the result in about a week from 10-weeks of gestational age. By using NIPT, we expect a reduction in the number of invasive studies and the risk of fetal loss. OBJECTIVE: To communicate the experience obtained at Genetics Clinic of the Hospital Angeles Lomas, in the use of NIPT by MPS as a method of prenatal screening for aneuploidies and fetal sex determination. MATERIAL AND METHODS: A prospective, observational and descriptive study was carried out in order to develop a database of patients who underwent NIPT (Harmony test) from August 2013 to date. Maternal blood samples were analyzed at Ariosa Diagnostics Inc. at San Jose California, USA. RESULTS: Noninvasive prenatal test was applied to 42 patients, with average maternal age of 37.1 years. The percentage of gestational age was 13.3 weeks and of fetal fraction was 12.7%. Two cases of high risk of trisomy 18 and two cases with high risk for X monosomy were obtained. In only one case the test was used for fetal determination, because of a story of Wiskott-Aldrich (W-A) disease. In all cases of low risk, the result was confirmed at birth and fetal sex was consistent with reports of literature. CONCLUSIONS: NIPT is currently the screening test with the highest detection rate (greater than 98%, with a false negative rate lesser than 0.5% and a sensitivity and specificity close to 100%), although it can vary from one chromosome to another. It is indicated for women with a result of high risk for trisomy 13, 18 and 21. This test has not been validated for low risk women or multiple pregnancies. In our series, the most frequent indication was advanced maternal age. The weight of the patients is important because it is a factor related to the percentage of fetal DNA. In cases with high risk for X monosomy in which the cytogenetic result was 46, XX, it is important to consider as much causes as possible, such as uniparental disomy (UPD), mosaicism and maternal contamination. Only in a case with W-A story the test was conducted specifically for fetal sex determination and confirmed by amniocentesis. In the cases of high-risk results, confirmation by an invasive method, before an obstetric decision, is indispensable. Further studies are still needed to continue the validation of this test by different molecular techniques and in other groups of patients.
Subject(s)
High-Throughput Nucleotide Sequencing/methods , Prenatal Diagnosis/methods , Trisomy/diagnosis , Adult , Aneuploidy , Female , Humans , Mexico , Middle Aged , Pregnancy , Prospective Studies , Sex Determination Analysis/methods , Young AdultABSTRACT
Miscarriage is the loss of pregnancy before 20 weeks of gestation and occurs in 15% of clinically recognized pregnancies. However, 5% of couples present recurrent abortion, which means more than two losses whether consecutive or not. One of the main causes of both, spontaneous and recurrent abortion, are genetic. Within it, chromosomal abnormalities are the most important. So far, the only risk factor that has been clearly defined is maternal age. Nevertheless, in patients with recurrent abortion, there has been research on some other factors that generate a greater predisposition to aneuploidy, and consequently, recurrent abortion risk. One of the mechanisms that may be the link between aneuploidy risk and maternal age is the level of Follicle Stimulating Hormone (FSH). This is due to the fact that elevated levels of Follicle Stimulating Hormone have been found to modify the morphology of meiotic spindles, which in turn leads to a higher risk of aneuploidy. In this article we present a literature review on the subject, as well as the case of a patient with two abortions, one of them with trisomy 13, and the other with trisomy 18.
Subject(s)
Abortion, Spontaneous/genetics , Chromosome Disorders/genetics , Trisomy/genetics , Adult , Aneuploidy , Chromosomes, Human, Pair 13/genetics , Chromosomes, Human, Pair 18/genetics , Female , Follicle Stimulating Hormone, Human/blood , Humans , Maternal Age , Middle Aged , Pregnancy , Pregnancy Trimester, First , Recurrence , Risk Factors , Trisomy 13 Syndrome , Trisomy 18 SyndromeABSTRACT
BACKGROUND: Duchenne muscular dystrophy (DMD) is the most frequent inherited and lethal neuromuscular disorder in humans. Molecular prenatal diagnosis of DMD through amniocentesis is a real preventive reproductive option in our country, although experience with chorionic villus sampling is still limited (CVS). OBJECTIVE: Perform the first prenatal diagnosis in an obligate DMD carrier woman in Mexico by CVS. MATERIAL AND METHOD: CVS was performed in an obligate DMD carrier woman in which no partial intragenic deletions were present but a haplotype at-risk was identified. Cytogenetic analysis with GTG banding was performed and genomic DNA extraction from CVS sample was done without culture. Fetal gender assignment was achieved by ultrasonography at 12 weeks of gestation and confirmed by PCR amplification of two Y chromosome-linked loci (SRY and DYS389I/II). Identification of the DMD haplotype at-risk in the fetus was done through analysis of the intragenic markers pERT87.8/TaqI and pERT87.15/Xmnl. RESULTS: Absence of PCR products corresponding to Y chromosome-linked loci in DNA CVS sample was compatible with a female fetus; it was confirmed later by cytogenetic study and prenatal ultrasound follow-up. Linkage analysis reveals that the female fetus inherited the DMD haplotype at-risk. We did not identify any maternal DNA contamination in CVS molecular analysis and these results were postnatally confirmed in DNA obtained from buccal cells. CONCLUSION: Molecular prenatal diagnosis through chorionic villus sampling could be an early reproductive prevention strategy applicable to Duchenne/Becker muscular dystrophy carrier women in our country.
Subject(s)
Chorionic Villi Sampling , Muscular Dystrophy, Duchenne/pathology , Adult , Alleles , Female , Humans , Molecular Diagnostic Techniques , Muscular Dystrophy, Duchenne/genetics , PedigreeABSTRACT
Introducción: Las anormalidades cromosómicas son una causa frecuente de morbilidad y mortalidad en la población humana. Objetivo: Describir el número y tipo de las alteraciones cromosómicas numéricas y estructurales detectadas en estudios citogenéticos realizados prenatalmente y en recién nacidos en el Instituto Nacional de Perinatología (INPer) durante el periodo comprendido de enero a diciembre del 2003. Metodología: Realizar un estudio descriptivo de tipo retrolectivo de los pacientes revisados por el Departamento de Genética con defectos congénitos que presentaron anormalidades cromosómicas. Resultados: Durante el año 2003, 3.26% (189/5795) de los pacientes nacidos en el INPer presentaron defectos al nacimiento, de los cuales veintisiete pacientes mostraron un cariotipo anormal de los cuales 21 (77.7%) presentaron alteraciones cromosómicas numéricas; además, en seis (22.2%) se encontró una alteración cromosómica estructural, lo que representa 0.46% de los pacientes nacidos en el INPer. En seis casos el diagnóstico se realizó en etapa prenatal y se corroboró al nacimiento. Conclusiones: La mayoría de alteraciones cromosómicas se presentan con múltiples defectos al nacimiento y con alteración en el crecimiento y desarrollo mental. Es importante que ante la presencia de pacientes con múltiples defectos mayores estructurales se sospechen este tipo de alteraciones y se realicen los estudios necesarios a la familia para poder brindar un adecuado asesoramiento genético.
Introduction: Chromosomal anomalies are a frequent cause of human disease. Objective: Describe the numerical and structural chromosomal anomalies detected by cytogenetic studies done prenatally and in newborns found in the Instituto Nacional de Perinatología during the period between January and December 2003. Methods: Descriptive study of the patients with congenital defects seen by the Genetics Department who presented chromosomal anomalies. Results: During the year 2003, the 3.46% (189/5795) of the babies born at the INPer had structural anomalies. Twenty patients had a chromosomal anomaly of which 21 (77.7%) had a chromosomal numeric alteration and six (22.2%) a chromosomal structural anomaly which represented 0.46% of the newborns. In six cases the diagnosis was done prenatally and confirmed at birth. Conclusions: Most of the chromosomal anomalies present themselves with multiple congenital anomalies and retarded growth and development. It is very important to implement this type of studies in patients with congenital anomalies, complete the familiar study and provide an accurate genetic counseling to the parents.
ABSTRACT
Background. Minor facial anomalies in 14-33 percent of exposed fetuses have been associated with the teratogenic effect of antiepileptic drugs (AED) since 1968. The purpose of this article is to describe the facial characteristics ofoffspring of non-epileptic women previously describen in the literature, and to correlate the facial anomalies with the specific drug. Methods. An interval was defined where 95 percent as "uncommon values" (UV) or as being in the "alert zone"; the odds ratio with Wolf modification was used and then Fisher's tes for comparison with healthy newborns. Full-term eutrophic newborns of epileptic mothers who received attention at the epilepsy clinic of a gyneco-obstetric center were included. Results. During the study period, 72 eutrophic, full-term newborns were included; in 70 cases at least one measurement was found in the alert zone, with a predominance of the mid-line area. No differences were found between neonates who received monotherapy vs. polytherapy. The groups exposed to phenobarbital, clonazepam and multiple AED showed more uncommon values (p <0.05), identified as minor dysmorphisms by other authors. It seems to be a particulat susceptibility of the mid-line of the face to show the effects of AED and, additionally, of environmental agents. Conclusions. No differences were found in the facial values among the different AED used in monotherapy form. It is suggested that the choice of drug used during pregnancy must be decided on according to the clinical dignosis of each mother's epilepsy, and not on the basis of ptential teratogenic risk
Subject(s)
Humans , Female , Infant, Newborn , Abnormalities, Drug-Induced/diagnosis , Epilepsy/pathology , Face/abnormalities , Mothers , Anthropometry , Case-Control Studies , Epilepsy/drug therapy , PregnancyABSTRACT
Las alteraciones cromosómicas explican un tercio de la etiología genética de los trastornos de la reproducción; el objetivo del estudio fue determinar la frecuencia de las alteraciones de los sexocromosomas (SC) en población mestiza con amenorrea, esterilidad e infertilidad en el Instituto Nacional de Perinatología. Se realizaron estudios citogenéticos en el laboratorio de Genética en muestras de sangre periférica del 1 de enero de 1984 al 31 de diciembre de 1995, con indicación de amenorrea, esterilidad, infertilidad o antecedente de hijo con defecto congénito sugestivo de cromosopatía y se correlacionaron con los hallazgos clínicos. Se revisaron las fórmulas cromosómicas de 3,201 cariotipos realizados en sangre periférica: se detectaron 61 pacientes con alteración de los sexocromosomas, predominando los mosaicos. Las alteraciones de SC se encontraron en 1.5 por ciento de las pacientes estudiadas y deben considerarse dentro de la etiología al estudiar esterilidad e infertilidad
Subject(s)
Humans , Male , Female , Adolescent , Adult , Infertility, Female/genetics , Infertility, Male/genetics , Karyotyping , Mosaicism , Sex Chromosome Aberrations/geneticsABSTRACT
La precencia de epilepsia en una mujer embarazada plantea una mayor probabilidad de complicaciones del binomio madre-hijo por el uso de medicamentos antiepilépticos (MAE) y/o la epilepsia misma. Un grupo de 100 pacientes embarazadas con epilepsia fueron estudiadas prospectivamente en forma clínica (obstétrica, neurológica y genética) y con determinación de niveles séricos (NS) de los MAE. En 61 se utilizó monoterapia y 18 no recibieron MAE. Los fármacos más utilizados fueron fenitoína (41), carbamazepina (35) y valproato. Los NS de los MAE estuvieron en la mayoría de los casos dentro o abaja de rangos recomendados con adecuado control clínico; sólo en 10 de los casos se informó una mayor calidad de crisis. El desvelo y la suspensión del medicamento fueron causas frecuentes asociadas al descontrol epiléptico. Las complicaciones obstétricas similares a las encontradas en mujeres embarazadas sanas. El 50 por ciento culminó en operación cesárea por indicación obstétrica (sólo tres por recomendaciones neurológica). No se detectaron malformaciones mayores y 12 por ciento cursaron con dismorfias menores. Este estudio muestra la evolución obstétrico-neurológica de un grupo de 100 pacientes mexicanas con epilepsia y embarazo en un hospital de tercer nivel de atención y se hace hincapié en el manejo farmacológico, las complicaciones y el riesgo teratogénico.
Subject(s)
Pregnancy , Humans , Female , Valproic Acid/administration & dosage , Valproic Acid/adverse effects , Carbamazepine/administration & dosage , Carbamazepine/adverse effects , Drug Combinations , Epilepsy , Phenytoin/administration & dosage , Phenytoin/adverse effects , Pregnancy Complications , Prospective StudiesABSTRACT
Dentro del efecto teratogénico de los fármacos antiepilépticos, se han asociado las dismorfias faciales
