OBJECTIVE: To explore the genetic etiology of fetuses with congenital anomalies of the kidney and urinary tract (CAKUT) by whole exome sequencing (WES). METHODS: WES was performed on DNA extracted from cord blood samples of 26 fetuses with unexplained CAKUT with/without other structural anomalies. In the first 19 cases, sequencing was performed on fetal DNA only, and the turnaround time was 11-12 weeks. For the remaining 7 cases, the fetus and its parents were sequenced simultaneously, and the turnaround time was 8-9 weeks. RESULTS: Of the 26 cases, pathogenic variants were identified in 4 (15.4%) cases, which respectively involved UMOD, NEK8, HNF1B, and BBS2 genes, and likely pathogenic variants were identified in 2 (7.7%) cases, which respectively involved HSPD1 and GRIN2B genes. Two of the 4 cases had other anomalies in addition to CAKUT. Thus, the detection rate was only 2/19 (10.5%) for isolated CAKUT and 4/7 (57.1%) for CAKUT with additional anomalies. CONCLUSION The application of WES as a prenatal diagnostic approach for CAKUT fetuses with or without other anomalies allowed early and accurate diagnosis and improved their clinical management.
Exome ; Female ; Fetus ; Humans ; Kidney ; pathology ; Pregnancy ; Urinary Tract ; pathology ; Urogenital Abnormalities ; genetics ; Whole Exome Sequencing

We performed an immunohistochemical study on the estrogen receptor alpha (ER-alpha) distribution in the cerebellum of a human neonate with multiple congenital anomalies, that had been acquired during autopsy. Although the exact pathology in the brain was not clearly elucidated in this study, an unidentified stressful condition might have induced the astrocytes into reactive states. In this immunohistochemical study on the neonatal cerebellum with multiple congenital anomalies, intense ER-alpha immunoreactivities (IRs) were localized mainly within the white matter even though ER-alpha IRs were known to be mainly localized in neurons. Double immunohistochemical staining showed that ER-alpha IR cells were reactive astrocytes, but not neurons. Interestingly, there were differences in the process length among the reactive astrocytes showing ER-alpha IRs. Our quantitative data confirmed that among the glial fibrillary acidic protein (GFAP)-expressing reactive astrocytes, the cells exhibiting intense ER-alpha IRs have much longer cytoplasmic processes and relatively weaker GFAP IRs. Taken together, the elongated processes of reactive astrocytes might be due to decreased expression of GFAP, which might be induced by elevated expression of ER-alpha even though the elucidation of the exact mechanism needs further studies.
Abnormalities, Multiple/*pathology ; Astrocytes/*metabolism ; Autopsy ; Brain/pathology ; Cerebellum/*metabolism ; Cytoplasm/metabolism ; Estrogen Receptor alpha/*metabolism ; Female ; Gastrointestinal Diseases/congenital/*pathology ; *Gene Expression Regulation ; Glial Fibrillary Acidic Protein/metabolism ; Humans ; Immunohistochemistry/methods ; Infant, Newborn ; Urogenital Abnormalities/*pathology

Adult ; Azoospermia/pathology* ; Carbonic Anhydrases/genetics* ; Congenital Abnormalities/genetics* ; Epithelial Sodium Channels/genetics* ; Gene Expression Regulation/genetics* ; Genome, Human ; Humans ; Infertility, Male/genetics* ; Male ; Male Urogenital Diseases/genetics* ; Mutation ; Vas Deferens/abnormalities*

OBJECTIVETo explore the feasibility of serial slices microscopic histological investigation for the elaborate evaluation of reproductive system malformations.

METHODSNewborn male mice prenatally exposed to different doses of subcutaneously given diethylstilbestrol (DES) from gestational day 9 to 17 were treated by fixing parts of the abdomen in situ and setting them to transected serial slices. All the slices were stained, studied under the microscope and serially recorded by software. The gubernaculum was morphologically analyzed and its location and size were measured.

RESULTSMorphologically, the gubernaculum could be identified clearly, its structure inhomogeneous from proximal to distal and dissymmetric from right to left. The environmental estrogen produced different effects on the morphology of the gubernaculum in different parts and most obviously affected its length.

CONCLUSIONPrenatal exposure to environmental estrogen has evident and general effects on the gubernacular development of newborn male mice. The morphological study with serial histological slices gives a precise and systematic evaluation of genital malformations.

Animals ; Animals, Newborn ; Carcinogens ; toxicity ; Diethylstilbestrol ; toxicity ; Female ; Gestational Age ; Male ; Mice ; Mice, Inbred Strains ; Pregnancy ; Prenatal Exposure Delayed Effects ; Testis ; anatomy & histology ; drug effects ; Urogenital Abnormalities ; chemically induced ; pathology