RESUMO
El término diagnóstico prenatal comprende todas las modalidades de diagnóstico dirigidas a detectar durante la gestación una anomalía congénita que incluya trastornos estructurales o funcionales. Un porcentaje de las mismas se debe a factores genéticos. El presente documento pretende detallar las indicaciones actuales de las pruebas invasivas y de las no invasivas, describir las pruebas de laboratorio que se utilizan en el diagnóstico prenatal de alteraciones genéticas y proponer esquemas de trabajo para el estudio de estas alteraciones genéticas
The term prenatal diagnosis includes all diagnostic modalities aimed at detecting a congenital anomaly during pregnancy that includes structural or functional disorders. A percentage of them are due to genetic factors. This document intends to detail the current indications of invasive and non-invasive tests, describe the laboratory tests used in the prenatal diagnosis of genetic alterations, and propose work schemes for the study of these genetic alterations
Assuntos
Humanos , Testes Genéticos/métodos , Diagnóstico Pré-Natal/métodos , Doenças Genéticas Inatas/diagnóstico , Transtornos Cromossômicos/diagnóstico , Marcadores Genéticos/genética , Aneuploidia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Fatores de Risco , Padrões de Prática MédicaRESUMO
Introduction and objective: Noonan syndrome (NS) is a genetic disorder characterized by a wide range of distinctive features and health problems. It caused in 50% of cases by missense mutations in PTPN11 gene. It has been postulated that it is possible to predict the disease course based into the impact of mutations on the protein. Patients and methods: We report two cases of severe NS phenotype including hydrops fetalis. PTPN11 gene was studied in germinal cells of both patients by sequencing. Results: Two different mutations (p.Gly503Arg and p.Met504Val) was detected in PTPN11 gene. Discussion: These mutations have been reported previously, and when they were germinal variants, patients presented classic NS, NS with other malignancies and recently, p.Gly503Arg has been also observed in a patient with severe NS and hydrops fetalis, as our cases. Therefore, these observations shade light on that it is not always possibly to determine the genotype-phenotype relation based into the impact of mutations on the protein in NS patients with PTPN11 mutations
Introducción y objetivo: El síndrome de Noonan (SN) es un trastorno genético caracterizado por una amplia gama de signos distintivos y problemas de salud. Está causado en el 50% de los casos por mutaciones missense en el gen PTPN11. Se ha postulado que es posible predecir el curso de la enfermedad en función del impacto de las mutaciones en la proteína. Pacientes y métodos: Presentamos 2 casos de fenotipo severo de SN con hydrops fetalis. En ambos casos se realizó la secuenciación del gen PTPN11 en células germinales. Resultados: Se identificaron 2 mutaciones diferentes en dicho gen (p.Gly503Arg y p.Met504Val). Discusión: Estas mutaciones ya han sido identificadas previamente, y cuando se presentan en línea germinal, los pacientes pueden presentar SN clásico, SN con alteraciones malignas o recientemente, p.Gly503Arg se ha observado en un paciente con SN e hydrops fetalis, como los 2 casos que presentamos. Por tanto, estas observaciones muestran, que en pacientes con SN y mutaciones en el gen PTPN11, no es siempre posible determinar la relación genotipo-fenotipo en función del impacto de la mutación en la proteína
Assuntos
Humanos , Síndrome de Noonan/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Fenótipo , Mutação/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismoRESUMO
INTRODUCTION AND OBJECTIVE: Noonan syndrome (NS) is a genetic disorder characterized by a wide range of distinctive features and health problems. It caused in 50% of cases by missense mutations in PTPN11 gene. It has been postulated that it is possible to predict the disease course based into the impact of mutations on the protein. PATIENTS AND METHODS: We report two cases of severe NS phenotype including hydrops fetalis. PTPN11 gene was studied in germinal cells of both patients by sequencing. RESULTS: Two different mutations (p.Gly503Arg and p.Met504Val) was detected in PTPN11 gene. DISCUSSION: These mutations have been reported previously, and when they were germinal variants, patients presented classic NS, NS with other malignancies and recently, p.Gly503Arg has been also observed in a patient with severe NS and hydrops fetalis, as our cases. Therefore, these observations shade light on that it is not always possibly to determine the genotype-phenotype relation based into the impact of mutations on the protein in NS patients with PTPN11 mutations.
