Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 47
Filter
1.
Clin Genet ; 105(1): 87-91, 2024 01.
Article in English | MEDLINE | ID: mdl-37619988

ABSTRACT

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. The affected fetus had multiple malformations, including posterior neck edema, micrognathia, low-set and small ears, auricular hypoplasia, cleft lip and palate, short extremities, and a combination of rarely occurring pre- and postaxial polydactyly. Genome sequencing identified compound heterozygous variants in the RAB34 gene: maternal c.254T>C, p.(Ile85Thr), and paternal c.691C>T, p.(Arg231*) variants. Only the paternal variant was present in the unaffected sibling. Evidence in the literature indicated that Rab34-/- mice displayed a ciliopathy phenotype with cleft palate and polydactyly. These features were consistent with malformations detected in our patient supporting the pathogenicity of the identified RAB34 variants. Overall, this case report further expands genetic landscape of human ciliopathy syndromes and suggests RAB34 as a candidate gene for skeletal ciliopathies.


Subject(s)
Abnormalities, Multiple , Ciliopathies , Cleft Lip , Cleft Palate , Polydactyly , Humans , Animals , Mice , Cleft Palate/diagnostic imaging , Cleft Palate/genetics , Ciliopathies/diagnostic imaging , Ciliopathies/genetics , Ciliopathies/pathology , Polydactyly/genetics , Abnormalities, Multiple/genetics , Syndrome , rab GTP-Binding Proteins/genetics
2.
Pediatr Dev Pathol ; 26(5): 494-498, 2023.
Article in English | MEDLINE | ID: mdl-37672683

ABSTRACT

Hereditary connective tissue disease is known to cause aortic lesions at an early age. Familial aortic aneurysm/dissection is caused due to an ACTA2 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. The patient presented with severe left heart failure, extensive dissection from the ascending aorta to the common iliac artery, and myocardial and cerebral infarctions. He underwent an urgent Bentall surgery. Six months later, the patient underwent surgical reconstruction of the abdominal aorta from the aortic arch and returned to normal daily activities. Pathological examination demonstrated the absence of elastic fibers but presence of abundant reticular fibers and mucopolysaccharides from the tunica intima to the media. Genetic testing revealed a heterozygous missense variant of the ACTA2 gene. To the best of our knowledge, this is the first sporadic case of structurally abnormal smooth muscle organization resulting in clinical symptoms with no previously reported pathogenicity.


Subject(s)
Aortic Aneurysm, Thoracic , Aortic Dissection , Male , Humans , Adolescent , Aortic Dissection/genetics , Aortic Dissection/surgery , Mutation , Mutation, Missense , Aortic Aneurysm, Thoracic/diagnosis , Aortic Aneurysm, Thoracic/genetics , Aortic Aneurysm, Thoracic/surgery , Actins/genetics
3.
Neuropathology ; 43(2): 190-196, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36325654

ABSTRACT

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. Both brains showed polymicrogyria, multiple subarachnoidal, subcortical, and subventricular heterotopia resulting from abnormal proliferation of neural stem/progenitor cells, cell differentiation, and migration of neuroblasts. Scattered cell nests immunoreactive for phosphorylated-S6 ribosomal protein (P-RPS6) (Ser240/244) were observed in the polymicrogyria-like cortical plate, intermediate zone, and arachnoid space, suggesting that the PI3K-AKT-MTOR pathway was actually activated in these cells. Pathological analyses could shed light on the mechanisms involved in disrupted brain development in the somatic mosaicism of the PI3K-AKT-MTOR pathway.


Subject(s)
Hemimegalencephaly , Polymicrogyria , Humans , Hemimegalencephaly/genetics , Hemimegalencephaly/metabolism , Hemimegalencephaly/pathology , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Polymicrogyria/metabolism , Polymicrogyria/pathology , Mosaicism , TOR Serine-Threonine Kinases/metabolism , Brain/pathology , Mutation
4.
Diagnostics (Basel) ; 11(10)2021 Oct 04.
Article in English | MEDLINE | ID: mdl-34679535

ABSTRACT

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. The CRITO-NIPT results were compared with the genetic results. In cases of test discrepancies, the placentae were collected for detailed genetic research, and the pre-procedure fetal ultrasound findings were referred to. RESULTS: The positive predictive value of T21, T18, and T13 was 93.55%, 88.46%, and 100%, respectively. In 90% of the of false positive (FP) cases, the placentae were examined. In 75% of the CRITO FP-T21 cases, placental mosaicism, or a demised twin's T21, were confirmed. There were complicated mosaic cases, including tetrasomy 21/trisomy7 and monosomy 21/trisomy21 cases. In one of three no-call cases, an intermediate deletion of chromosome 13 was detected. CONCLUSIONS: The CRITO study investigated the mechanism of false positives, and the detailed mechanisms in mosaic and no-call cases. There have hitherto been no reports that have provided insight by partitioning the placenta to compare the NIPT and invasive test results, nor that have provided detailed ultrasound findings in the cases of discordant results, revealing the demonstrated importance of, and necessity for, detailed ultrasonography. This article describes the potential of rolling-circle replication as a powerful biosensing platform, as well as the importance of examining the fetus in detail with ultrasound. However, we should remember that the potential applications raise ethical and social concerns that go beyond aneuploidy and its methodology.

5.
Genes (Basel) ; 12(3)2021 03 02.
Article in English | MEDLINE | ID: mdl-33801456

ABSTRACT

The phosphatase and tensin homolog (PTEN) 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 PTEN mutation have been found, so far. We encountered a rare case of fetal PTEN mutation. Fetal macrocephaly was noted at 16 weeks. At 18 and 20 weeks, neurosonography revealed megalencephaly with an asymmetrical structure and multifocal polygyria. The head circumference (HC) was +6.2 SD at 18 weeks and +8.1 SD at 20 weeks. The parents opted for pregnancy termination, and the male fetus was delivered at 21 weeks, with HC +9.3 SD. Single-nucleotide polymorphism (SNP) array for amniotic cells showed paternal uniparental disomy (UPD) 10q mosaicism, and the mosaic ratio was calculated as 56% from B-allele frequency. Exome sequencing revealed the pathogenic PTEN mutation with mosaicism. The heterozygous PTEN mutation may not cause early manifestations from the fetal period, and an abnormal phenotype may appear after birth. This may be the reason why fetal defects associated with PTEN mutation are not detected. Since this case had homozygous and heterozygous mutations, survival was possible, exhibiting an incredibly huge head with cortical dysplasia from early pregnancy.


Subject(s)
Malformations of Cortical Development/diagnostic imaging , Megalencephaly/diagnostic imaging , PTEN Phosphohydrolase/genetics , Trisomy/genetics , Uniparental Disomy/genetics , Abortion, Induced , Chromosomes, Human, Pair 10/genetics , Female , Humans , Male , Malformations of Cortical Development/genetics , Megalencephaly/genetics , Mosaicism , Mutation , Paternal Inheritance , Polymorphism, Single Nucleotide , Pregnancy , Pregnancy Trimester, Second
6.
Diagnostics (Basel) ; 11(2)2021 Feb 18.
Article in English | MEDLINE | ID: mdl-33670620

ABSTRACT

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. First, we conducted a preliminary experiment to compare the original PGT-A method to our modified method. Based on the preliminary results, we decided to implement the modified strategy without whole-genome amplification (WGA) and combined it with three analytical software packages. Next, we conducted a prospective study with 824 samples. According to the indication for invasive tests, the D-karyo positive rates were 2.5% and 5.0%, respectively, in the screening positive group with NT ≥ 3.5 mm and the group with fetal abnormalities by ultrasound. D-karyo is a breakthrough modality that can detect submicroscopic CNVs ≥ 1.0 Mb accurately in only 10.5 h for 24 samples at a low cost. Implementing D-karyo as a prenatal rapid screening test will reduce unnecessary CMA and achieve more accurate prenatal genetic testing than G-banding.

7.
Am J Med Genet A ; 170A(4): 908-17, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26782913

ABSTRACT

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. DNA microarray was used to investigate the duplication/triplication region of 16 cases. Although there was no overlapping region common to all 26 cases, the 1q41-qter region was frequently involved. One case diagnosed as a pure interstitial trisomy of chromosome 1q by G-banded karyotype analysis was instead found to be a pure partial tetrasomy by CytoScan HD Array. In four 1q trisomy syndrome cases involving translocation, the translocated partner chromosome could not be detected by DNA microarray analyzes despite G-banded karyotype analysis, because there were a limited number of probes available for the partner region. DNA microarray and G-banded karyotyping techniques were therefore shown to be compensatory diagnostic tools that should be used by clinicians who suspect chromosomal abnormalities. It is important to continue recruiting affected patients and observe and monitor their symptoms to reveal genotype-phenotype correlations and to fully understand their prognosis and identify causal regions of symptoms.


Subject(s)
Chromosome Deletion , Chromosome Duplication , Chromosomes, Human, Pair 1 , Genetic Association Studies , Adolescent , Adult , Child , Child, Preschool , Chromosome Banding , Chromosome Disorders/diagnosis , Chromosome Disorders/genetics , Comparative Genomic Hybridization , Facies , Humans , Infant , Male , Phenotype , Syndrome , Young Adult
8.
Am J Med Genet A ; 158A(12): 3148-58, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23165946

ABSTRACT

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 8p23.1. We confirm a region involved in both diaphragmatic and heart malformations. Results from a novel CNVConnect algorithm, prioritizing protein-protein interactions between products of genes in the 8p23.1 hotspot and products of previously known CDH causing genes, implicated GATA4, NEIL2, and SOX7 in diaphragmatic defects. Sequence analysis of these genes in 226 chromosomally normal CDH patients, as well as in a small number of deletion 8p23.1 patients, showed rare unreported variants in the coding region; these may be contributing to the diaphragmatic phenotype. We also demonstrated that two of these three genes were expressed in the E11.5-12.5 primordial mouse diaphragm, the developmental stage at which CDH is thought to occur. This combination of bioinformatics and expression studies can be applied to other chromosomal hotspots, as well as private microdeletions or microduplications, to identify causative genes and their interaction networks.


Subject(s)
Hernias, Diaphragmatic, Congenital , Animals , Chromosome Deletion , Chromosomes, Human, Pair 8/genetics , Chromosomes, Human, Pair 8/metabolism , DNA/blood , DNA/genetics , DNA Glycosylases/genetics , DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics , Female , GATA4 Transcription Factor/genetics , Heart Defects, Congenital/blood , Heart Defects, Congenital/genetics , Heart Defects, Congenital/metabolism , Hernia, Diaphragmatic/blood , Hernia, Diaphragmatic/genetics , Hernia, Diaphragmatic/metabolism , Humans , Karyotyping , Mice , Mice, Inbred C57BL , Phenotype , Pregnancy , Protein Interaction Maps , SOXF Transcription Factors/genetics
9.
J Clin Biochem Nutr ; 51(3): 196-203, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23170047

ABSTRACT

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. Since alendronate is suggested to increase the risk of non-steroidal anti-inflammatory drug-related gastropathy, we hypothesized that bisphosphonates and non-steroidal anti-inflammatory drugs have the same pathophysiological mechanisms in gastrointestinal mucosa: Bisphosphonates may induce cellular lipid peroxidation by inducing the production of mitochondrial superoxide. We also hypothesized that geranylgeranylacetone, an antiulcer drug, may prevent lipid peroxidation by reducing superoxide production. We treated gastric RGM1 cells and small intestinal IEC6 cells with alendronate or risedronate, and examined cellular injury, lipid peroxidation and superoxide production with specific fluorescent dyes, and underwent electron paramagnetic resonance spectroscopy to detect the production of superoxide in vitro. The results indicated that bisphosphonates indeed induced cellular injury, cellular lipid peroxidation, and superoxide production. We also demonstrated that the pretreatment of geranylgeranylacetone decreased superoxide production and prevented cellular lipid peroxidation. These results suggested that bisphosphonates, like non-steroidal anti-inflammatory drugs, induce lipid peroxidation by producing mitochondrial superoxide, which was prevented by geranylgeranylacetone.

10.
Digestion ; 85(2): 131-5, 2012.
Article in English | MEDLINE | ID: mdl-22269294

ABSTRACT

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. We hypothesized that gastric acid and NSAID treatment synergistically induce cellular injury in gastric epithelial cells. We treated gastric epithelial RGM1 cells with acidic solutions and NSAIDs, and examined cellular injury, lipid peroxidation, mitochondrial transmenbrane potential and mitochondrial superoxide. We pretreated RGM1 cells with the acidic solutions for 0.5 h and after that treated them with each NSAID for 15 h and found that the exposure to acid and NSAIDs indeed induced cellular injury. We hypothesized that gastric acid and NSAID treatment synergistically induce mitochondrial superoxide production, which induces gastric cellular injury.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Gastric Mucosa/drug effects , Lipid Peroxidation/drug effects , Mitochondria/drug effects , Stomach Ulcer/physiopathology , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cell Culture Techniques , Cell Survival/drug effects , Epithelial Cells , Gastric Acid , Gastric Mucosa/physiopathology , Hydrogen-Ion Concentration , Mitochondria/physiology , Rats , Stomach Ulcer/chemically induced , Superoxides/metabolism
11.
Am J Med Genet A ; 155A(11): 2879-84, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21990267

ABSTRACT

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;q26.1). The patient showed upward gazing and tonic seizure of lower extremities followed by generalized clonic seizures at 4 months of age. Electroencephalogram showed hypsarrhythmia when asleep. By using fluorescent in situ hybridization (FISH), southern hybridization and inverse PCR, the translocation breakpoints were determined at the nucleotide level. The 5q14.3 breakpoint was localized 121.5-kb upstream of MEF2C. The 15q26.2 breakpoint was mapped 119-kb downstream of LOC91948 non-coding RNA. We speculate that the translocation may disrupt the proper regulation of MEF2C expression in the developing brain, resulting in severe intellectual disability and early-onset epileptic encephalopathy.


Subject(s)
Chromosomes, Human, Pair 5/genetics , Epilepsy/genetics , Intellectual Disability/genetics , MADS Domain Proteins/genetics , Myogenic Regulatory Factors/genetics , Translocation, Genetic , Abnormal Karyotype , Agenesis of Corpus Callosum/genetics , Blotting, Southern , Child , Child, Preschool , Chromosome Breakpoints , Cloning, Molecular , Electroencephalography , Epilepsy/physiopathology , Female , Humans , In Situ Hybridization, Fluorescence , Infant , Intellectual Disability/physiopathology , MADS Domain Proteins/metabolism , MEF2 Transcription Factors , Magnetic Resonance Imaging , Myogenic Regulatory Factors/metabolism , Physical Chromosome Mapping , RNA, Untranslated/genetics , Seizures/genetics , Seizures/physiopathology
12.
Am J Med Genet A ; 155A(12): 2925-32, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22009788

ABSTRACT

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 5.0-5.7 Mb and 6.6 Mb 6p terminal deletions, respectively, and FOXC1 was apparently deleted in both patients. In the other patient, the inversion breakpoint at 6p25 was estimated to be in or very close to the FOXC1 locus, but DNA array analysis did not reveal a deletion around the breakpoint. Common extraocular findings in these patients included broad forehead, brachycephaly, hypertelorism, downslanting palpebral fissures, small anteverted nose, and cardiac defects. Two patients also exhibited autistic characteristics. The two patients with deletions exhibited poor muscle tone and developmental delays. Most of these extraocular findings were similar to those found in previous patients with FOXC1 mutations and distinct from those found in patients with PITX2 mutations, who frequently develop umbilical and dental anomalies. We suggest that the psychomotor retardation is a clinical manifestation associated with a deletion of multiple contiguous genes in the 6p terminus and that this phenomenon is similar to the 6p25 deletion syndrome. Understanding the relationship between genetic lesions and the spectrum of extraocular findings in patients with Axenfeld-Rieger anomalies may lead to better clinical management.


Subject(s)
Chromosome Aberrations , Chromosomes, Human, Pair 6 , Eye Abnormalities/genetics , Anterior Eye Segment/abnormalities , Child, Preschool , Chromosome Banding , Comparative Genomic Hybridization , Eye Abnormalities/diagnosis , Eye Diseases, Hereditary , Female , Forkhead Transcription Factors/genetics , Humans , Infant , Infant, Newborn , Male , Phenotype
13.
J Clin Biochem Nutr ; 49(1): 25-30, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21765603

ABSTRACT

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. We found that the lansoprazole pretreatment significantly reduced cellular injury, maintained mitochondrial transmembrane potential, and decreased lipid peroxidation. Furthermore, the signal intensity of the electron spin resonance spectrum of the indomethacin-treated mitochondria which were pretreated with lansoprazole showed considerable reduction compared to those without the lansoprazole pretreatment. These results suggest that lansoprazole reduced superoxide production in the mitochondria of indomethacin treated cells, and subsequently inhibited lipid peroxide and cellular injury in gastric epithelial cells.

14.
J Gastroenterol ; 46(10): 1167-76, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21789481

ABSTRACT

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. METHODS: Firstly we treated gastric epithelial RGM1 cells with solutions containing various concentrations of HCl (i.e., of varying pH), and examined cellular injury, lipid peroxidation, and apoptosis with specific fluorescent dyes. Secondly, we performed electron paramagnetic resonance (EPR) spectroscopy of isolated, acid-exposed mitochondria from the cells, using a spin-trapping reagent for superoxide, 5-(2,2-dimethyl-1,3-propoxy cyclophosphoryl)-5-methyl-1-pyrroline N-oxide (CYPMPO). Finally, we established novel RGM1 cells that overexpressed manganese superoxide dismutase (MnSOD), which removes superoxide from mitochondria, and examined the effect of acid treatment on cellular membrane lipid peroxidation. RESULTS: The results indicated that the exposure to acid indeed induced cellular injury, cellular lipid peroxidation, apoptosis, and the demonstration of the exact superoxide spectra on EPR spectroscopy in gastric epithelial cells, and that overexpression of MnSOD decreased superoxide production and prevented cellular lipid peroxidation. CONCLUSION: These results suggested that gastric acid, like nonsteroidal anti-inflammatory drugs (NSAIDs), induces mitochondrial superoxide production, which induces gastric cellular injury by triggering cellular lipid peroxidation and apoptosis.


Subject(s)
Epithelial Cells/metabolism , Gastric Acid/physiology , Gastric Mucosa/pathology , Mitochondria/metabolism , Animals , Apoptosis , Cell Line , Electron Spin Resonance Spectroscopy , Gastric Mucosa/metabolism , Hydrochloric Acid/administration & dosage , Hydrochloric Acid/toxicity , Hydrogen-Ion Concentration , Lipid Peroxidation/physiology , Membrane Potential, Mitochondrial/physiology , Rats , Superoxide Dismutase/metabolism , Superoxides/metabolism
15.
J Clin Biochem Nutr ; 48(2): 107-11, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21373261

ABSTRACT

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. However, recent clinical demonstrated the prevalence of non-steroidal anti-inflammatory drugs-induced small intestinal mucosal injury is more often than previously expected. In this review, we discuss the defense mechanisms of stomach, and the pathophysiology of non-steroidal anti-inflammatory drugs-induced injury of stomach and small intestine, especially focused on non-steroidal anti-inflammatory drugs' action on mitochondria.

16.
J Obstet Gynaecol Res ; 36(3): 671-5, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20598055

ABSTRACT

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. Two-dimensional ultrasound examination revealed unexplained polyhydramnios and a male fetus. Fetal biometry showed shortened long bones. Three-dimensional ultrasonography clearly demonstrated a hypoplastic nose with a depressed nasal bridge and contracture of wrists and fingers. Chromosome analysis of the amniotic fluid cells revealed the 46,Y,del(X)(p22.3) karyotype. Fluorescence in situ hybridization revealed a deletion of subtelomeric sequences at the Xpter and STS gene, but not a deletion of the KAL gene. The genomic copy number analysis demonstrated terminal deletion of 8.33 Mb that included SHOX, CSF2RA, XG, ARSE, NLGN4 and STS genes. We think that our case presents typical features of a fetus with this disorder and will be of great help in prenatal ultrasound diagnosis.


Subject(s)
Chondrodysplasia Punctata/diagnosis , Chondrodysplasia Punctata/genetics , Chromosome Deletion , Chromosomes, Human, X/genetics , Biometry , Female , Humans , In Situ Hybridization, Fluorescence , Male , Pregnancy , Prenatal Diagnosis
19.
J Hum Genet ; 53(10): 914-919, 2008.
Article in English | MEDLINE | ID: mdl-18685808

ABSTRACT

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 0.7-Mb resolution). Chromosomal abnormalities were found in six patients (10%): 46,XY,der(13)t(12;13)(p12.1; p11).ish del(5)(p11p12); 46,XY, ish del(17)(p12p12); 46,XX.ish dup(11)(p13p13); and 46,X,idic(Y)(q11.2); and in two cases, mos 45,X/46XX. Autosomal abnormalities in three cases are likely to be pathogenic, and sex chromosome abnormalities in three follow previous findings. It is noteworthy that 10% of patients with schizophrenia have (sub)microscopic chromosomal abnormalities, indicating that genome-wide copy number survey should be considered in genetic studies of schizophrenia.


Subject(s)
Chromosome Aberrations , Nucleic Acid Hybridization/methods , Oligonucleotide Array Sequence Analysis/methods , Schizophrenia/genetics , Chromosomes, Artificial, Bacterial , Female , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Male
SELECTION OF CITATIONS
SEARCH DETAIL
...