RESUMEN
BACKGROUND: NLRP7 mutations are responsible for recurrent molar pregnancies and associated reproductive wastage. To investigate the role of NLRP7 in sporadic moles and other forms of reproductive wastage, the authors sequenced this gene in a cohort of 135 patients with at least one hydatidiform mole or three spontaneous abortions; 115 of these were new patients. METHODS/RESULTS: All mutations were reviewed and their number, nature and locations correlated with the reproductive outcomes of the patients and histopathology of their products of conception. The presence of NLRP7 mutations was demonstrated in two patients with recurrent spontaneous abortions, and some rare non-synonymous variants (NSVs), present in the general population, were found to be associated with recurrent reproductive wastage. These rare NSVs were shown to be associated with lower secretion of interleukin 1ß and tumour necrosis factor and therefore to have functional consequences similar to those seen in cells from patients with NLRP7 mutations. The authors also attempted to elucidate the cause of stillbirths observed in 13% of the patients with NLRP7 mutations by examining available placentas of the stillborn babies and live births from patients with mutations or rare NSVs. A number of severe to mild placental abnormalities were found, all of which are known risk factors for perinatal morbidity. CONCLUSIONS: The authors recommend close follow-up of patients with NLRP7 mutations and rare NSVs to prevent the death of the rare or reduced number of babies that reach term.
Asunto(s)
Aborto Habitual/genética , Aborto Espontáneo/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Predisposición Genética a la Enfermedad , Mutación/genética , Reproducción/genética , Alelos , Estudios de Casos y Controles , Análisis Mutacional de ADN , Femenino , Estudios de Asociación Genética , Humanos , Mola Hidatiforme/genética , Interleucina-1beta/metabolismo , Leucocitos Mononucleares/metabolismo , Proteínas Mutantes/metabolismo , Mutación Missense/genética , Mortalidad Perinatal , Placenta/anomalías , Placenta/metabolismo , Placenta/patología , Embarazo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Women with Turner syndrome (TS) are at risk of premature ovarian failure. The objective of this retrospective study was to identify patients with TS who could be potential candidates for fertility preservation and to determine their present reproductive and fertility status. Criteria for fertility preservation included: (i) spontaneous menarche; (ii) confirmation by ultrasound examination of the presence of at least one normal ovary; and (iii) serum FSH concentrations below 40 IU/l. Using the Montreal Children's Hospital Cytogenetic Database from 1990 to 2006, 28 patients with complete or partial absence of one X chromosome were identified: 13 (46%) were 45,X; nine (32%) had mosaic karyotypes; and six (21%) had karyotypes containing isochromosome or ring X chromosome. Six patients (21%) had spontaneous pubertal development and four (14%) were identified as potential candidates for fertility preservation. One underwent an ovarian stimulation protocol of gonadotrophin-releasing hormone agonist down-regulation followed by recombinant FSH and human menopausal gonadotrophin stimulation. Two metaphase-II-stage oocytes were aspirated and vitrified using the McGill Cryoleaf vitrification system. Another patient conceived spontaneously at the age of 24 years. In conclusion, fertility preservation may not be feasible for most patients with TS. However, after careful consideration of increased pregnancy-associated risks, fertility preservation may be offered to young females with mosaic TS.
