RESUMO
Cystic fibrosis is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene. This disorder produces a variable phenotype including lung disease, pancreatic insufficiency, and meconium ileus plus bilateral agenesis of the vas deferens causing obstructive azoospermia and male infertility. Preimplantation genetic diagnosis is an alternative that allows identification of embryos affected by this or other genetic diseases. We report a case of couple with cystic fibrosis; the woman had the I148 T mutation and the man had the Delta F508 gene mutation. The couple underwent in vitro fertilization, associated with preimplantation genetic diagnosis, and with subsequent selection of healthy embryos for uterine transfer. The result was an uneventful pregnancy and delivery of a healthy male baby.
Assuntos
Fibrose Cística/diagnóstico , Fertilização in vitro/métodos , Mutação , Diagnóstico Pré-Implantação/métodos , Adulto , Biópsia , Blastocisto/patologia , Fibrose Cística/embriologia , Fibrose Cística/genética , Feminino , Humanos , Masculino , Ilustração Médica , Gravidez , Resultado da Gravidez , Resultado do TratamentoRESUMO
Cystic fibrosis is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene. This disorder produces a variable phenotype including lung disease, pancreatic insufficiency, and meconium ileus plus bilateral agenesis of the vas deferens causing obstructive azoospermia and male infertility. Preimplantation genetic diagnosis is an alternative that allows identification of embryos affected by this or other genetic diseases. We report a case of couple with cystic fibrosis; the woman had the I148 T mutation and the man had the Delta F508 gene mutation. The couple underwent in vitro fertilization, associated with preimplantation genetic diagnosis, and with subsequent selection of healthy embryos for uterine transfer. The result was an uneventful pregnancy and delivery of a healthy male baby.
A fibrose cística é uma doença autossômica recessiva causada por mutações no gene regulador de condutância transmembrana na fibrose cística. Produz fenótipo variável, incluindo doença pulmonar, insuficiência pancreática, íleo meconial, além de agenesia bilateral dos ductos deferentes, causando azoospermia obstrutiva e infertilidade masculina. O diagnóstico genético pré-implantacional é uma alternativa diagnóstica, que permite identificar embriões portadores de fibrose cística e outras doenças genéticas. Relatamos o caso de um casal portador de fibrose cística, sendo a mulher portadora da mutação I148 T e o homem da mutação gênica Delta F508. O casal foi submetido a técnicas de fertilização in vitro associadas ao diagnóstico genético pré-implantacional, com consequente seleção de embriões saudáveis, que foram transferidos para o útero, resultando em gravidez sem intercorrências e com feto saudável, do sexo masculino.
Assuntos
Adulto , Feminino , Humanos , Masculino , Gravidez , Fibrose Cística/diagnóstico , Fertilização in vitro/métodos , Mutação , Diagnóstico Pré-Implantação/métodos , Biópsia , Blastocisto/patologia , Fibrose Cística/embriologia , Fibrose Cística/genética , Ilustração Médica , Resultado da Gravidez , Resultado do TratamentoRESUMO
INTRODUCTION: The high genetic heterogeneity in populations with a wide spectrum of mutations in the CF transmembrane conductance regulator gene (CFTR), makes the detection of mutations a very hard and difficult task, thereby limiting the accurate diagnosis of the disease, mainly in patients with uncharacterized mutations. MATERIAL AND METHODS: Molecular strategies, like targeted identification of the most frequent CFTR mutations in Mexican population combined with linkage analysis using markers, is very useful for carrier detection and for prenatal diagnosis in affected families with CF. In this paper we show that the combination of methodologies was a crucial alternative to reach a precise prenatal CF diagnosis. We documented CF diagnosis in a 14th-week fetus combining the screening of the most common mutations in Mexican population with linkage analysis of two extragenic polymorphisms (XV2C/TaqI and KM19/PstI). RESULTS: We determined that the fetus inherited the PG542X mutation from its mother and an unknown mutation from its father through the chromosomal phases analysis.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/diagnóstico , Diagnóstico Pré-Natal , Criança , Fibrose Cística/embriologia , Fibrose Cística/genética , Análise Mutacional de DNA , Feminino , Ligação Genética , Haplótipos , Heterozigoto , Humanos , Masculino , México/epidemiologia , Linhagem , Polimorfismo de Fragmento de Restrição , GravidezRESUMO
Cystic Fibrosis (CF) is a severe and relatively common autosomic recessive disease caused by a variety of mutations in the CFTR gene. The most frequent mutation worldwide, consists of the deletion of the phenylalanine codon at position 508 (delta F508). Here we report the first cases of prenatal diagnosis of CF by DNA analysis in couples at risk in Venezuela. The study focused on the detection of delta F508 alleles analyzing DNA recovered directly from amniocytes or from their cultures, using the polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis. Two of three fetuses resulted homozygotic for the delta F508 allele and the third one turned out to be a delta F508 carrier. This information sustained the genetic counseling of the couples and allowed them to take objective reproductive decisions, a direct consequence of the availability of gene analysis at the DNA level.