RESUMEN
Although a rare disease, bilateral congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage kidney disease in children. Ultrasound-based prenatal prediction of postnatal kidney survival in CAKUT pregnancies is far from accurate. To improve prediction, we conducted a prospective multicenter peptidome analysis of amniotic fluid spanning 140 evaluable fetuses with CAKUT. We identified a signature of 98 endogenous amniotic fluid peptides, mainly composed of fragments from extracellular matrix proteins and from the actin binding protein thymosin-ß4. The peptide signature predicted postnatal kidney outcome with an area under the curve of 0.96 in the holdout validation set of patients with CAKUT with definite endpoint data. Additionally, this peptide signature was validated in a geographically independent sub-cohort of 12 patients (area under the curve 1.00) and displayed high specificity in non-CAKUT pregnancies (82 and 94% in 22 healthy fetuses and in 47 fetuses with congenital cytomegalovirus infection respectively). Change in amniotic fluid thymosin-ß4 abundance was confirmed with ELISA. Knockout of thymosin-ß4 in zebrafish altered proximal and distal tubule pronephros growth suggesting a possible role of thymosin ß4 in fetal kidney development. Thus, recognition of the 98-peptide signature in amniotic fluid during diagnostic workup of prenatally detected fetuses with CAKUT can provide a long-sought evidence base for accurate management of the CAKUT disorder that is currently unavailable.
Asunto(s)
Enfermedades Renales , Sistema Urinario , Anomalías Urogenitales , Líquido Amniótico , Animales , Niño , Femenino , Humanos , Riñón/diagnóstico por imagen , Péptidos , Embarazo , Estudios Prospectivos , Anomalías Urogenitales/diagnóstico por imagen , Pez CebraAsunto(s)
Anoftalmos/genética , Atresia Esofágica/genética , Enfermedades de los Genitales Femeninos/genética , Proteínas HMGB/genética , Mosaicismo , Factores de Transcripción/genética , Anoftalmos/patología , Ojo/patología , Femenino , Enfermedades Fetales/genética , Enfermedades Fetales/patología , Enfermedades de los Genitales Femeninos/congénito , Humanos , Mutación , Fenotipo , Embarazo , Factores de Transcripción SOXB1 , SíndromeRESUMEN
We describe two cases of sonographic abnormalities associated with unusual chromosomal aberrations. Case 1 presented with a cystic hygroma at 12 weeks' gestation. Cytogenetic analysis revealed an unbalanced complex chromosome rearrangement implicating chromosomes 6, 13 and 21 (karyotype: 47,XX,t(6;21;14)(q14;q21;q21)mat,+21) and corresponding to a complete trisomy 21. This anomaly resulted from malsegregation of a maternal balanced three-way translocation. For case 2, an alobar holoprosencephaly was identified by ultrasonography at 23 weeks' gestation. Chromosomal analysis showed a recombinant rec (13), dup q chromosome, secondary to unequal crossing-over of a paternal pericentric inversion of chromosome 13, giving rise to partial trisomy 13q (karyotype: 46,XX,rec(13)dup(13q)inv(13)(p11q21)pat). These two cases illustrate the role of ultrasound in leading to detection not only of foetal chromosomal aberrations but also of rare balanced chromosomal rearrangements presented by one of the two parents.
