RESUMEN
BACKGROUND: The high frequency of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene mutation p.Arg117His in patients with congenital bilateral absence of the vas deferens (CBAVD) and in newborns screened for CF has created a dilemma. METHODS: Phenotypic and genotypic data were retrospectively collected in 179 non-newborn French individuals carrying p.Arg117His and a second CFTR mutation referred for symptoms or family history, by all French molecular genetics laboratories, referring physicians, CF care centres and infertility clinics. RESULTS: 97% of the patients had the intronic T7 normal variant in cis with p.Arg117His. 89% patients were male, with CBAVD being the reason for referral in 76%. In 166/179 patients with available detailed clinical features, final diagnoses were: four late-onset marked pulmonary disease, 83 isolated CBAVD, 67 other CFTR-related phenotypes, including 44 CBAVD with pulmonary and/or pancreatic symptoms and 12 asymptomatic cases. Respiratory symptoms were observed in 30% of the patients, but the overall phenotype was mild. No correlation was observed between sweat chloride concentrations and disease severity. Five couples at risk of CF offspring were identified and four benefited from prenatal or preimplantation genetic diagnoses (PND or PGD). Eight children were born, including four who were compound heterozygous for p.Arg117His and one with a severe CF mutation. CONCLUSIONS: Patients with CBAVD carrying p.Arg117His and a severe CF mutation should benefit from a clinical evaluation and follow-up. Depending on the CBAVD patients' genotype, a CFTR analysis should be considered in their partners in order to identify CF carrier couples and offer PND or PGD.
Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Fibrosis Quística/genética , Enfermedades Urogenitales Masculinas/genética , Diagnóstico Prenatal , Niño , Preescolar , Fibrosis Quística/complicaciones , Fibrosis Quística/patología , Femenino , Heterocigoto , Humanos , Lactante , Recién Nacido , Infertilidad Masculina/complicaciones , Infertilidad Masculina/genética , Masculino , Enfermedades Urogenitales Masculinas/complicaciones , Enfermedades Urogenitales Masculinas/patología , Mutación , Tasa de Mutación , Fenotipo , Sudor/química , Conducto Deferente/anomalías , Conducto Deferente/patologíaAsunto(s)
Retardo del Crecimiento Fetal/genética , Placenta/fisiopatología , Trisomía/genética , Adulto , Muestra de la Vellosidad Coriónica , Cromosomas Humanos Par 16/genética , Femenino , Retardo del Crecimiento Fetal/sangre , Retardo del Crecimiento Fetal/diagnóstico , Humanos , Recién Nacido de Bajo Peso/sangre , Recién Nacido de Bajo Peso/fisiología , Recién Nacido , Masculino , Pruebas de Detección del Suero Materno , Mosaicismo , Embarazo , Resultado del Embarazo , Proteína Plasmática A Asociada al Embarazo/análisis , Diagnóstico Prenatal , Trisomía/diagnósticoRESUMEN
Innovative biotechnical progress over the past few years regards stem cells and therapeutic cloning, which open promising medical horizons for many presently incurable diseases. THE CURRENT DEBATE: The research work in France has been stalled because of the prohibitions listed in the so-called "bioethical" laws of 1994. The ongoing revision of these laws is based on a certain number of ethical questions and launches a disputable parlementary debate. Other than reproductive cloning and research on the embryo, the possibilities provided by stem cells and therapeutic cloning should be emphasized and the different positions advanced specified, showing an evolution in the laws in France. ABUSIVE LEGISLATIVE PROHIBITIONS: The proposed law, which maintains the prohibition for research on the embryo, with a 5-Year dispensation, and which explicitly prohibits therapeutic cloning, is not in keeping with the widening of in this field expected by research teams. Many scientists and physicians, supported by patients' associations, are aware of the importance of therapeutic progress attached to such research. They should not be stalled in their studies by the prohibitions maintained in the new law.