Aortic Dissection and a Previously Unreported Missense Variant Mutation in a Young Patient: A Case Report.

Hereditary connective tissue disease is known to cause aortic lesions at an early age. Familial aortic aneurysm/dissection is caused due to an mutation that affects smooth muscle structure. We present a case of a 15-year-old boy with a mild developmental disorder in whom no abnormalities were identified on previous physical examinations.

Compound heterozygous variants in RAB34 in a rare skeletal ciliopathy syndrome.

Skeletal ciliopathies are a heterogenous group of congenital disorders characterized by multiple internal abnormalities, and distinct radiographic presentation. Pathogenic variants in at least 30 cilia genes are known to cause skeletal ciliopathies. Here we report a fetus with an atypical skeletal ciliopathy phenotype and compound heterozygous variants in the RAB34 gene.

Somatic mosaicism of the PI3K-AKT-MTOR pathway is associated with hemimegalencephaly in fetal brains.

It is known that somatic activation of PI3K-AKT-MTOR signaling causes malformations of cortical development varying from hemimegalencephaly to focal cortical dysplasia. However, there have been few reports of fetal cases. Here we report two fetal cases of hemimegalencephaly, one associated with mosaic mutations in PIK3CA and another in AKT1.

Clinical Validation of Fetal cfDNA Analysis Using Rolling-Circle-Replication and Imaging Technology in Osaka (CRITO Study).

Background: Noninvasive prenatal genetic testing (NIPT) has been adopted as the first choice for aneuploidy screening. The purposes of this study were to investigate the accuracy of Vanadis NIPT (hereafter CRITO-NIPT) in order to gain a deeper insight into the reasons for discrepancies, as well as to discuss the role of fetal ultrasound.

Methods: Between 2019 and 2020, CRITO-NIPT was performed in 1218 cases of patients who underwent CVS or amniocentesis after a detailed fetal ultrasound exam and genetic counseling.

Fetal Megalencephaly with Cortical Dysplasia at 18 Gestational Weeks Related to Paternal UPD Mosaicism with Mutation.

The phosphatase and tensin homolog () gene is a tumor-suppressor gene located on 10q22-23. Since the introduction of molecular genetics in prenatal diagnostics, various birth defects associated with gene mutations have been diagnosed. However, no reports on fetal cases related to mutation have been found, so far.

D-karyo-A New Prenatal Rapid Screening Test Detecting Submicroscopic CNVs and Mosaicism.

Chromosomal microarray analysis (CMA), recently introduced following conventional cytogenetic technology, can detect submicroscopic copy-number variations (CNVs) in cases previously diagnosed as "cytogenetically benign". At present, rapid and accurate chromosomal analysis is required in prenatal diagnostics, but prenatal CMA is not widely used due to its high price and long turnaround time. We introduced a new prenatal screening method named digital karyotyping (D-karyo), which utilizes a preimplantation genetic test for the aneuploidy (PGT-A) platform.

Detailed analysis of 26 cases of 1q partial duplication/triplication syndrome.

Partial 1q trisomy syndrome is a rare disorder. Because unbalanced chromosomal translocations often occur with 1q trisomy, it is difficult to determine whether patient symptoms are related to 1q trisomy or other chromosomal abnormalities. The present study evaluated genotype-phenotype correlations of 26 cases diagnosed with 1q partial trisomy syndrome.

Bisphosphonate-induced gastrointestinal mucosal injury is mediated by mitochondrial superoxide production and lipid peroxidation.

Bisphosphonates such as alendronate and risedronate are commonly used for the treatment of postmenopausal osteoporosis. They have the gastrointestinal adverse effects such as erosions and ulcers in stomach and small intestine. However, the detailed biological mechanism remains to be elucidated.

Congenital diaphragmatic hernia interval on chromosome 8p23.1 characterized by genetics and protein interaction networks.

Chromosome 8p23.1 is a common hotspot associated with major congenital malformations, including congenital diaphragmatic hernia (CDH) and cardiac defects. We present findings from high-resolution arrays in patients who carry a loss (n = 18) or a gain (n = 1) of sub-band 8p23.

Rebamipide attenuates nonsteroidal anti-inflammatory drugs (NSAID) induced lipid peroxidation by the manganese superoxide dismutase (MnSOD) overexpression in gastrointestinal epithelial cells.

Nonsteroidal anti-inflammatory drugs (NSAIDs) often cause gastrointestinal complications such as gastric ulcers and erosions. Recent studies on the pathogenesis have revealed that NSAIDs induce lipid peroxidation in gastric epithelial cells by generating superoxide anion in mitochondria, independently with cyclooxygenase-inhibition and the subsequent prostaglandin deficiency. Although not clearly elucidated, the impairment of mitochondrial oxidative phosphorylation, or uncoupling, by NSAIDs is associated with the generation of superoxide anion.

NSAIDs and acidic environment induce gastric mucosal cellular mitochondrial dysfunction.

Non-steroidal anti-inflammatory drugs (NSAIDs) often cause gastrointestinal complications such as gastric ulcers and erosions. Recent studies on the pathogenesis have revealed that NSAIDs induce lipid peroxidation in gastric epithelial cells by generating superoxide in mitochondria, independently with cyclooxygenase inhibition and the subsequent prostaglandin deficiency. More recently, gastric hydrochloric acid (HCl) has been regarded as an inciting factor of gastric mucosal injuries, and reportedly induced cellular lipid peroxidation in vitro.

Axenfeld-Rieger anomaly and Axenfeld-Rieger syndrome: clinical, molecular-cytogenetic, and DNA array analyses of three patients with chromosomal defects at 6p25.

Clinical phenotypes of and genetic aberrations in three unrelated Japanese patients with Axenfeld-Rieger anomalies and various accompanying malformations of systemic organs are described. GTG-banded chromosome analysis showed terminal deletions of the short arm of chromosome 6 in two patients and an inversion, inv(6)(p25q14), in the other. FISH and DNA array analyses revealed that the two patients with deletions had 5.

De novo 5q14.3 translocation 121.5-kb upstream of MEF2C in a patient with severe intellectual disability and early-onset epileptic encephalopathy.

Recent studies have shown that haploinsufficiency of MEF2C causes severe intellectual disability, epilepsy, hypotonia, and cerebral malformations. We report on a female patient with severe intellectual disability, early-onset epileptic encephalopathy, and hypoplastic corpus callosum, possessing a de novo balanced translocation, t(5;15)(q13.3;q26.

Gastric acid induces mitochondrial superoxide production and lipid peroxidation in gastric epithelial cells.

Background: Gastric hydrochloric acid (HCl) has been regarded as an inciting factor in gastric mucosal injuries and has been reported to induce lipid peroxidation in vitro. However, because HCl is not an oxidant per se, the exact mechanism by which the acid induces lipid peroxidation is unknown. We hypothesized that gastric acid may disrupt mitochondrial transmembrane potential and induce the production of superoxide in mitochondria, which subsequently may induce lipid peroxidation and apoptosis in gastric mucosal cells.

Lansoprazole inhibits mitochondrial superoxide production and cellular lipid peroxidation induced by indomethacin in RGM1 cells.

Lansoprazole is effective in healing non-steroidal anti-inflammatory drugs induced ulcers, and antioxidant properties have been thought to play a key role in healing ulcers. We hypothesize that lansoprazole exerts a cytoprotective effect by inhibiting reactive oxygen species leakage from mitochondria and lipid peroxidation. We pretreated gastric epithelial RGM1 cells with lansoprazole and then treated them with indomethacin in vitro.

The pathophysiology of non-steroidal anti-inflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine.

Non-steroidal anti-inflammatory drugs are the most commonly prescribed drugs for arthritis, inflammation, and cardiovascular protection. However, they cause gastrointestinal complications. The pathophysiology of these complications has mostly been ascribed to non-steroidal anti-inflammatory drugs' action on the cyclooxygenase inhibition and the subsequent prostaglandin deficiency.

Maternal uniparental isodisomy and heterodisomy on chromosome 6 encompassing a CUL7 gene mutation causing 3M syndrome.

We report a case of segmental uniparental maternal hetero- and isodisomy involving the whole of chromosome 6 (mat-hUPD6 and mat-iUPD6) and a cullin 7 (CUL7) gene mutation in a Japanese patient with 3M syndrome. 3M syndrome is a rare autosomal recessive disorder characterized by severe pre- and postnatal growth retardation that was recently reported to involve mutations in the CUL7 or obscurin-like 1 (OBSL1) genes. We encountered a patient with severe growth retardation, an inverted triangular gloomy face, an inverted triangle-shaped head, slender long bones, inguinal hernia, hydrocele testis, mild ventricular enlargement, and mild mental retardation.

Prenatal findings in a fetus with contiguous gene syndrome caused by deletion of Xp22.3 that includes locus for X-linked recessive type of chondrodysplasia punctata (CDPX1).

The X-linked recessive type of chondrodysplasia punctata (CDPX1) is a skeletal disorder that is characterized by stippled calcification at an epiphyseal nucleus and the surrounding soft tissue, short stature and an unusual face because of nasal hypoplasia. In most of the patients, this condition is noted after birth because of a characteristic face or respiratory problems. Here, we report a fetus with CDPX1.

Microarray comparative genomic hybridization analysis of 59 patients with schizophrenia.

Schizophrenia is a common psychiatric disorder with a strong genetic contribution. Disease-associated chromosomal abnormalities in this condition may provide important clues, such as DISC1. In this study, 59 schizophrenia patients were analyzed by microarray comparative genomic hybridization (CGH) using custom bacterial artificial chromosome (BAC) microarray (4,219 BACs with 0.

Cellular membrane fluidity measurement by fluorescence polarization in indomethacin-induced gastric cellular injury in vitro.

Background: Gastric complications of indomethacin involve generation of reactive oxygen species, which induce gastric mucosal injury via lipid peroxidation of cell membranes. Peroxidation by reactive oxygen species alters the amounts of unsaturated fatty acids in the cell membrane and thus affects membrane fluidity. Indomethacin-induced lipid peroxidation can thus be detected by measuring cellular membrane fluidity by the fluorescence polarization (FP) method.

Neoplastic transformation and induction of H+,K+ -adenosine triphosphatase by N-methyl-N'-nitro-N-nitrosoguanidine in the gastric epithelial RGM-1 cell line.

N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces gastric cancer in animal models. We established an MNNG-induced mutant of the rat murine RGM-1 gastric epithelial cell line, which we named RGK-1, that could be used as an in vitro model of gastric cancer. This cell line showed signs of neoplasia and transformation, in that it lost contact inhibition and formed tumors in nude mice.