Identification and validation of DNA methylation changes in pre-eclampsia.

Introduction: Pre-eclampsia (PE) is a dangerous placental condition that can lead to premature labour, seizures and death of mother and infant. Several studies have identified altered placental DNA methylation in PE; however, there is widespread inconsistency between studies and most findings have not been replicated. This study aimed to identify and validate consistent differences in methylation across multiple PE cohorts.

Human Papillomavirus / Expression in Preeclampsia-Affected Placentae.

Whether HPV is causative of pregnancy complications is uncertain. E6 and E7 affect functions underling preeclampsia (PET) in cultured trophoblasts, but whether E6 and E7 is produced in the placenta is uncertain. Here, we investigated whether / was expressed in the placentae from pregnancies with PET, other pregnancy complications (fetal growth restriction (FGR) and diabetes mellitus), and uncomplicated pregnancies.

Ewing's Sarcoma with Extension into Superior Vena Cava and Right Atrium.

Ewing sarcoma is rarely shown to develop this intravascular extension so the decision of the initial treatment is more difficult. We report a 7-year-old boy of this sarcoma with extension into superior vena cava (SVC) and right atrium (RA), who was successfully treated with initial surgery. Intravascular extension was observed from the azygous vein to SVC and finally RA.

Laparoscopic subtotal colectomy for a patient with chronic idiopathic colonic pseudo-obstruction: Report of a case.

A 47-year-old male patient without a documented past medical history was referred to Sanno Hospital because of constipation and abdominal pain, which he had had for more than 5 years. Abdominal X-ray and CT scan showed an enlarged ascending colon from the cecum to the transverse colon, without apparent mechanical obstruction. The patient was diagnosed with chronic idiopathic colonic pseudo-obstruction, and because his symptoms were resistant to medication, surgical treatment was required.

Selective Ablation of Tumorigenic Cells Following Human Induced Pluripotent Stem Cell-Derived Neural Stem/Progenitor Cell Transplantation in Spinal Cord Injury.

Tumorigenesis is an important problem that needs to be addressed in the field of human stem/progenitor cell transplantation for the treatment of subacute spinal cord injury (SCI). When certain "tumorigenic" cell lines are transplanted into the spinal cord of SCI mice model, there is initial improvement of motor function, followed by abrupt deterioration secondary to the effect of tumor growth. A significant proportion of the transplanted cells remains undifferentiated after transplantation and is thought to increase the risk of tumorigenesis.

A novel truncating mutation in MYH3 causes spondylocarpotarsal synostosis syndrome with basilar invagination.

Spondylocarpotarsal synostosis syndrome (SCT) is a rare group of skeletal dysplasias, characterized by disproportionate short stature with a short trunk, abnormal segmentation of the spine with vertebral fusion, scoliosis and lordosis, carpal and tarsal synostosis, and mild facial dysmorphisms. While the majority of the cases show autosomal recessive inheritance, only a few cases of vertical transmissions, with MYH3 mutations, have been reported. Here we report a case with typical SCT, carrying a novel heterozygous mutation in MYH3.

Germline mutations and somatic inactivation of TRIM28 in Wilms tumour.

Wilms tumour is a childhood tumour that arises as a consequence of somatic and rare germline mutations, the characterisation of which has refined our understanding of nephrogenesis and carcinogenesis. Here we report that germline loss of function mutations in TRIM28 predispose children to Wilms tumour. Loss of function of this transcriptional co-repressor, which has a role in nephrogenesis, has not previously been associated with cancer.

A Novel Mutation in NKX2-1 Shows Dominant-Negative Effects Only in the Presence of PAX8.

To date, >100 mutations in NKX2-1 have been described. Most NKX2-1 mutations are assumed to result in brain-lung-thyroid syndrome through haploinsufficiency, and only five NKX2-1 mutations with dominant-negative effects have been reported so far. In this case report, an additional patient with brain-lung-thyroid syndrome is reported, carrying a novel heterozygous mutation, c.

The Mosaicism Ratio of 45,X May Explain the Phenotype in a Case of Mixed Gonadal Dysgenesis.

Some patients with mixed gonadal dysgenesis (MGD), whose prototypical karyotype is 45,X/46,XY, are known to manifest complications characteristic of Turner syndrome. We report a 16-year-old social male with MGD presenting with coarctation of the aorta, one of the common complications for Turner syndrome. At birth, the patient was found to have hypospadias, bifid scrotum, and cryptorchidism.

A Novel Case of Somatic Mutation in Pediatric-Onset Aldosterone-Producing Adenoma.

Aldosterone-producing adenoma (APA), a subtype of primary aldosteronism, is a common cause of secondary hypertension in adults. Somatic mutations have been identified in about 12%-80% of adult-onset APA. In contrast, there has been no previous reported case of pediatric-onset APA in whom a somatic mutation was confirmed.

The developmental programme for genesis of the entire kidney is recapitulated in Wilms tumour.

Wilms tumour (WT) is an embryonal tumour that recapitulates kidney development. The normal kidney is formed from two distinct embryological origins: the metanephric mesenchyme (MM) and the ureteric bud (UB). It is generally accepted that WT arises from precursor cells in the MM; however whether UB-equivalent structures participate in tumorigenesis is uncertain.

Syndromic disorder of sex development due to a novel hemizygous mutation in the carboxyl-terminal domain of .

Alpha-thalassemia/mental retardation syndrome X-linked (ATRX; OMIM #301040), which is caused by mutations in the gene, is characterized by alpha-thalassemia, distinct dysmorphic facies, psychomotor development delay and genital abnormalities. Here, we describe a neonatal case of syndromic disorder of sex development, harboring a novel hemizygous mutation, p.Asp2352fs*1 in the carboxyl-terminal domain of .

A novel de novo germline mutation Glu40Lys in AKT3 causes megalencephaly with growth hormone deficiency.

Germline or somatic gain-of-function mutations in the v-akt murine thymoma viral oncogene homolog 3 (AKT3) have been reported to cause syndromic megalencephaly. We describe a novel germline mutation, p.Glu40Lys, in AKT3.

A novel heterozygous intronic mutation in POU1F1 is associated with combined pituitary hormone deficiency.

POU class 1 homeobox 1 (POU1F1) regulates pituitary cell-specific gene expression of somatotropes, lactotropes, and thyrotropes. In humans, two POU1F1 isoforms (long and short isoform), which are generated by the alternative use of the splice acceptor site for exon 2, have been identified. To date, more than 30 POU1F1 mutations in patients with combined pituitary hormone deficiency (CPHD) have been described.

Novel heterozygous mutation in the extracellular domain of associated with Hartsfield syndrome.

Heterozygous kinase domain mutations or homozygous extracellular domain mutations in have been reported to cause Hartsfield syndrome (HS), which is characterized by the triad of holoprosencephaly, ectrodactyly and cleft lip/palate. To date, more than 200 mutations in have been described; however, only 10 HS-associated mutations have been reported thus far. We describe a case of typical HS with hypogonadotropic hypogonadism (HH) harboring a novel heterozygous mutation, p.

The Distribution and Cellular Lineages of XX and XY Cells in Gonads Associated with Ovotesticular Disorder of Sexual Development.

Individuals with a 46,XX/46,XY karyotype are categorized as ovotesticular disorder of sexual development (ODSD) and have gonads with either an ovary on one side and a testis on the other side or a mixed ovotestis. To examine the distribution of 46,XX and 46,XY cells in gonads of 3 patients with ODSD, FISH for X and Y chromosomes and immunohistochemistry for SOX9 and FOXL2 were carried out. FISH analysis showed that XX signals were present in Sertoli cells in the seminiferous tubules, while cells containing Y signals were seen in epithelia of ovarian follicles.

Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases.

The risk of tumorigenicity is a hurdle for regenerative medicine using induced pluripotent stem cells (iPSCs). Although teratoma formation is readily distinguishable, the malignant transformation of iPSC derivatives has not been clearly defined due to insufficient analysis of histology and phenotype. In the present study, we evaluated the histology of neural stem/progenitor cells (NSPCs) generated from integration-free human peripheral blood mononuclear cell (PBMC)-derived iPSCs (iPSC-NSPCs) following transplantation into central nervous system (CNS) of immunodeficient mice.

Gonadal macrophage infiltration in congenital lipoid adrenal hyperplasia.

Objective: Congenital lipoid adrenal hyperplasia (lipoid CAH) results in impairment of adrenal and gonadal steroidogenesis caused by STAR mutations. Our previous study revealed upregulation of genes associated with inflammatory or immune response and macrophage infiltration in the adrenal cortex of Star-knockout mice. This study aimed at investigating macrophage infiltration in the gonads from human patients with lipoid CAH.

SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7.

Adrenal hypoplasia is a rare, life-threatening congenital disorder. Here we define a new form of syndromic adrenal hypoplasia, which we propose to term MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) syndrome. By exome sequencing and follow-up studies, we identified 11 patients with adrenal hypoplasia and common extra-adrenal features harboring mutations in SAMD9.

Radiological findings of perivascular epithelioid cell tumour (PEComa) of the falciform ligament.

Perivascular epithelioid cell tumour (PEComa) encompasses a group of mesenchymal tumours composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. A subset of PEComa that typically arises from the falciform ligament and/or ligamentum teres is termed clear cell myomelanocytic tumour of the falciform ligament/ligamentum teres. To date, its imaging findings have not been described.

Identification of X monosomy cells from a gonad of mixed gonadal dysgenesis with a 46,XY karyotype: case report.

Mixed gonadal dysgenesis (MGD) is a disorder of sexual development that typically has a mosaic 45,X/46,XY karyotype. A 1-year-old infant with 46,XY identified by peripheral blood karyotype demonstrated clinical manifestations and gonadal pathologic features of MGD. Fluorescence in situ hybridization (FISH) for X and Y chromosomes and immunofluorescence for SRY along with testicular and ovarian lineage markers SOX9 and FOXL2, respectively, were performed on paraffin sections from the gonad to ascertain the somatic mosaic state for 45,X monosomy and 46,XY cells.

Neonatal necrotizing fasciitis of the scrotum caused by Streptococcus agalactiae.

We herein describe the case of a 27-day-old male infant who was brought to the emergency room for intermittent crying, and swelling of the left scrotum. Based on the clinical findings, necrotizing fasciitis was suspected, and surgical intervention was successfully completed within a few hours of admission. Streptococcus agalactiae type Ia was cultured from the drained abscess, and was considered the causative pathogen.

Membranoproliferative glomerulonephritis and C3 glomerulonephritis: frequency, clinical features, and outcome in children.

Aim: C3 glomerulonephritis (C3GN) is a recently described disease that is related to membranoproliferative glomerulonephritis (MPGN). We retrospectively compared the frequencies, clinical characteristics, treatment modalities, and outcomes of C3GN and MPGN in a cohort of Japanese children.

Methods: Children who were pathologically diagnosed with MPGN (type I or III) in our hospital were divided into two groups based on immunofluorescence imaging of renal biopsies: children with MPGN induced by classical complement pathway activation (classical MPGN) and children with C3GN.