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Biomedical subjects

I Teshima

Publications and source records attributed to I Teshima.

At least 19 recordsLinked to original sources
PubMed2005

Holoprosencephaly and cleidocranial dysplasia in a patient due to two position-effect mutations: case report and review of the literature.

Holoprosencephaly (HPE) is a genetically heterogeneous developmental field defect in which midline cleavage of the forebrain and craniofacial structures is impaired. Based on the analysis of HPE patients with chromosome rearrangements, at least six loci for the disorder have been assigned. The sonic hedgehog gene (SHH) at 7q36 has been identified as the HPE3 locus. Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal disorder characterized by clavicular, pelvic and dental anomalies. It is caused by mutations in the osteoblast-specific transcription factor CBFA1/RUNX2, which maps to 6p21. We report a 20-year-old female with premaxillary agenesis (part of the HPE spectrum), as well as skeletal abnormalities and impacted teeth reminiscent of CCD. She carries a de novo 6;7 reciprocal translocation, with breakpoints at 6p21.1 and 7q36. We have shown previously that the 7q36 breakpoint maps 15 kb telomeric to the 5' end of SHH, which explains the patient's HPE phenotype. Now, using fluorescence in situ hybridization, we have identified a P1 artificial chromosome clone 800 kb upstream of CBFA1/RUNX2 that spans the 6p breakpoint. We propose that the proband's complex phenotype is due to two position-effect (PE) mutations, one at each translocation breakpoint, which have altered the expression of the SHH and CBFA1/RUNX2 genes. The role of PE mutations in human disease is also reviewed.

Adult↗
PubMed2001

Velo-cardio-facial syndrome: Implications of microdeletion 22q11 for schizophrenia and mood disorders.

Velo-cardio-facial syndrome (VCFS) is a congenital malformation syndrome with variable phenotypic features that has been associated with chromosomal microdeletion 22q11.2. Psychiatric disorders have been reported to be highly prevalent in individuals with this syndrome, and the objective of this study was to assess the nature and extent of psychopathology among individuals with VCFS. We studied 20 children and adolescents with 22q11 deletions determined by fluorescence in situ hybridization (FISH). Control subjects were 11 nondeleted siblings who were the closest age match to the affected subjects. Both affected and control subjects were assessed using two standardized psychiatric research instruments. The results of this study confirmed the high rate of psychiatric disorders among VCFS subjects (60% of our subjects). Of the specific types of disorders, only mood disorders were significantly more common among VCFS subjects compared to sibling controls, with eight VCFS subjects having mood disorders compared with none of the control subjects (P<0.02). Three affected subjects had schizotypal traits comorbid with a mood disorder. In addition, disruptive behavior disorders were frequently diagnosed among VCFS subjects. Using a dimensional measure of psychopathology, significant differences between VCFS subjects and sibling controls were found on three scales: ADHD (P<0.02), separation anxiety (P<0.02), and depression (P<0.01). VCFS subjects were achieving significantly less well academically and requiring significantly more special educational assistance than sibling controls. Follow-up data were available on two subjects, both of whom had been diagnosed with schizophrenia. Further research on psychopathology in VCFS may provide a model of how a specific genetic defect can lead to the development of psychiatric disorders.

Abnormalities, Multiple↗
PubMed2001

Total resection of an intracerebral hemangioendothelioma in an infant. Case report and review of the literature.

Hemangioendotheliomas (HEs) are vasoformative tumors rarely seen in the CNS. Histopathological features determining aggressive phenotypes have not been well defined. Potential cytogenetic alterations in these tumors have not been previously reported. We present a 4-month-old male infant with a temporal lobe HE. Fluorescence in situ hybridization and spectral karyotype analysis revealed translocation of chromosome 11q23. This case constitutes the first report of a gross total resection of an intracerebral HE in the pediatric age group, and of potential cytogenetic alterations involved in its pathogenesis. Based on our report and review of the literature, we note a discrepancy between histopathological criteria of aggressive tumor biology and clinical behavior. Further study of chromosomal abnormalities may be helpful in defining factors associated with a higher risk of malignant behavior. We conclude that gross total resection is currently the best available treatment option for these tumors, regardless of histology.

Biomarkers, Tumor↗
PubMed2000

Analphoid 3qter markers.

Two cases of marker chromosomes derived from a non-centromeric location were studied to determine the characteristics of these markers with respect to the presence of functional centromeres and whether an associated phenotype could be described. The markers were characterized by fluorescence in situ hybridization and centromeric protein studies. Assessments were done to identify clinical features. Case 1 is a girl referred at age 1.5 years with swirly areas of hyperpigmentation, bilateral preauricular pits, hypotonia, developmental delay, and seizures. Case 2 is a male first evaluated as a newborn and then later during the first year of life. He had streaky hypopigmentation, right preauricular pit, accessory nipples, postaxial polydactyly, asymmetric cerebral ventricles, duplicated right kidney, a right pulmonary artery stenosis, and seizures. Mosaicism for an extra marker from the 3qter region was present in both cases. Both markers had a constriction near one end and were C-band negative. Centromeric protein studies indicated absence of CENP-B, presence of CENP-C (data for case 1 only), and presence of CENP-E. Marker chromosomes were thus identified with a chromosomal origin far from their usual centromeric region and yet appeared to have functional centromeres. These two cases did not permit a specific clinical phenotype to be ascribed to the presence of tetrasomy for 3q26.2 approximately 3q27.2-->3qter.

Autoantigens↗
PubMed1999

Analysis of chromosome 22q as an aid to the diagnosis of rhabdoid tumor: a case report.

Malignant rhabdoid tumor is a highly aggressive tumor of childhood that may present as a soft-tissue primary tumor. We report a soft-tissue neoplasm that was polyphenotypic by immunohistochemical expression of epithelial, mesenchymal, and neural markers and did not meet the criteria for any of the usual pediatric small round-cell tumors. The findings raised the diagnosis of rhabdoid tumor, leading to testing for WT1 mRNA and protein expression, which were positive, as has been reported for renal rhabdoid tumor. This tumor had the typical clinical behavior of rhabdoid tumor with therapy resistance and early tumor-related death. Multicolor spectral karyotyping of this neoplasm showed a balanced translocation between chromosomes 1 and 22 with breakpoints at 1p36 and 22q11-12. The latter region is commonly involved in rhabdoid tumor. This change was also identified by fluorescence in situ hybridization. This case suggests that studies of chromosome 22 may be required to distinguish rhabdoid tumor from other soft-tissue tumors.

Chromosomes, Human, Pair 22↗
PubMed1999

Primary Ewing's sarcoma of the skull in children. Utility of molecular diagnostics, surgery and adjuvant therapies.

Ewing's sarcoma (ES) of the skull is rare. Herein, we present 2 cases of ES that involved the cranium in young children. In one case, the lesion originated in the petrous temporal bone; in the other, the frontal bone. Both children were acutely compromised neurologically by signs and symptoms of raised intracranial pressure. In both cases, radiographs revealed massive tumors affecting the skull. Neurosurgical resection of the tumor was undertaken in both instances, and the diagnosis of ES was confirmed by immunohistochemistry, cytogenetic analysis (translocation 11;22), spectral karyotyping and RT-PCR (demonstration of a EWS/FLI1 fusion transcript). Following aggressive surgical resection, both children received intensive chemotherapy. No child has received radiation therapy. One child is alive and well 8 years after diagnosis without any evidence of residual disease. The other is currently undergoing chemotherapy for her tumor. The principles involved in the management of children with cranial-based ES are discussed. These 2 cases serve to illustrate the fact that even children with massive ES tumors of the cranium may be salvaged with aggressive combination therapy.

Acute Disease↗
PubMed1999

Central neurocytoma: morphological, flow cytometric, polymerase chain reaction, fluorescence in situ hybridization, and karyotypic analyses. Case report.

The results of cytogenetic and molecular genetic analysis of a central neurocytoma are presented. Central neurocytomas are intriguing neoplasms that exhibit primarily neuronal, but also glial characteristics, which indicate an origin from a pluripotential neuroglial precursor. The authors describe an intraventricular neurocytoma in an 11-year-old boy that showed anaplastic features with widespread necrosis and mitoses, as well as extensive calcification and foci that exhibited marked neuronal differentiation with clusters of ganglion cells. Immunohistochemical examination showed prominent synaptophysin and neurofilament positivity and focal glial fibrillary acidic protein positivity. Electron microscopy revealed abundant neuritic processes with microtubules and dense core granules as well as mature ganglion cells. Flow cytometry studies revealed increased S (7.8%) and G2M (9.7%) phase components. Molecular and cytogenetic studies were undertaken to assess whether there were similarities to two other tumor types that exhibit neuronal differentiation, the neuroblastoma and medulloblastoma. Polymerase chain reaction and fluorescence in situ hybridization (FISH) analysis revealed no evidence of amplification of the MYCN oncogene or chromosome 1p deletion, which are common in neuroblastomas. Chromosomal analysis by G banding revealed a complex karyotype, with counts in the near-diploidy range (45-48). Two chromosomes 1 appeared normal on G banding and FISH analysis, with p58 signals present on the distal p arm of both chromosomes 1; however, three additional copies of distal 1q were present in rearrangements with 4 and 7. Although the histological findings indicate a kinship to the neuroblastoma and medulloblastoma, the central neurocytoma appears to have a different karyotypic profile, although more cases need to be assessed using molecular genetic analysis.

Brain Neoplasms↗
PubMed1998

Monozygotic twins with 45,X/46,XY mosaicism discordant for phenotypic sex.

We report on two sets of monozygotic twins (MZTs) discordant for phenotypic sex ascertained at birth when the female twin was noted to have signs of the Ullrich-Turner syndrome. Cytogenetic investigations on the female of the first pair showed 45,X/46,XY mosaicism in lymphocytes but fibroblasts grown from two skin biopsies at separate sites and from gonadal tissue showed only 45,X cells. The male showed mosaicism in both blood lymphocytes and skin fibroblasts. In the second family, both twins also showed mosaicism in lymphocytes. The female had a 45,X karyotype in fibroblasts from skin and gonadal tissue, but in contrast to the first family, the male twin had a normal male karyotype in fibroblasts from skin biopsy and from connective tissue adjacent to the vas deferens. Discordant phenotypic sex in monozygotic twins is rare. As in our cases, the nine previously reported sets of MZTs all had mosaicism for sex chromosome abnormalities. A mitotic error leading to the loss of a Y chromosome prior to, accompanying, or following the twinning process would account for the reported combinations of karyotypes.

Female↗
PubMed1997

Omphalocele in Miller-Dieker syndrome: expanding the phenotype.

We report on a patient prenatally diagnosed with omphalocele, mild cerebral ventriculomegaly, nuchal fold thickening, and cystic changes in the umbilical cord who was found postnatally to have lissencephaly type I. Prenatal chromosome analysis showed a normal male karyotype; however, postnatal high resolution banding and FISH analysis, using a probe for locus D17S379 in chromosome region 17p13.3, demonstrated a deletion at 17p13.3 consistent with Miller-Dieker syndrome (MDS). A review documented four more cases with MDS/isolated lissencephaly/17p-, with omphalocele. Because MDS is a contiguous gene disorder, we speculate that a gene or genes in this region have a major role in the closure of the lateral folds or the return of the midgut from the body stalk to the abdomen at 5-11 weeks of gestation. Prenatal diagnosis of omphalocele with mild ventriculomegaly should prompt FISH analysis for a deletion in 17p13.3.

Abnormalities, Multiple↗
PubMed1996

FISH detection of chromosome 15 deletions in Prader-Willi and Angelman syndromes.

We have evaluated fluorescence in situ hybridization (FISH) analysis for the clinical laboratory detection of the 15q11-q13 deletion seen in Prader-Willi syndrome (PWS) and Angelman syndrome (AS) using probes for loci D15S11, SNRPN, D15S10, and GABRB3. In a series of 118 samples from patients referred for PWS or AS, 29 had deletions by FISH analysis. These included two brothers with a paternally transmitted deletion detectable with the probe for SNRPN only. G-banding analysis was less sensitive for deletion detection but useful in demonstrating other cytogenetic alterations in four cases. Methylation and CA-repeat analyses of 15q11-q13 were used to validate the FISH results. Clinical findings of patients with deletions were variable, ranging from newborns with hypotonia as the only presenting feature to children who were classically affected. We conclude that FISH analysis is a rapid and reliable method for detection of deletions within 15q11-q13 and whenever a deletion is found, FISH analysis of parental chromosomes should also be considered.

Angelman Syndrome↗
PubMed1993

Molecular characterization of cytogenetic alterations associated with the Beckwith-Wiedemann syndrome (BWS) phenotype refines the localization and suggests the gene for BWS is imprinted.

To define the region of 11p15 involved in Beckwith-Wiedemann syndrome (BWS), we have carried out a molecular genetic analysis of six patients with features of BWS and constitutional cytogenetic abnormalities involving chromosome band 11p15. Molecular analysis confirmed the 11p origin of the duplicated material and defined the smallest region of overlap for such duplications, within which a gene involved in BWS must be located. This region encompasses the beta-globin gene complex (HBB) to 11pter. In both of our informative cases, the 11p duplication was found to be of paternal origin. Two BWS associated balanced translocations of 11p15 were studied to localize the breakpoints on 11p15. Somatic cell hybrids, Southern blotting and fluorescent in situ hybridization (FISH) showed that both breakpoints were between D11S12 and the insulin-like growth factor 2 (IGF2) gene. A non-BWS translocation breakpoint was more proximal, between HBB and calcitonin-A (CALCA). Pedigree analysis showed that both BWS associated 11p15 translocations were transmitted by phenotypically normal mothers. The data are compatible with the hypothesis that the BWS gene is imprinted and that the maternally inherited BWS gene is normally suppressed whereas the paternally inherited allele is active. Thus, duplications of paternal origin would lead to increased dosage of the BWS gene. Similarly increased dosage of the BWS gene could account for the findings in maternally inherited 11p15 translocations by altering normal imprinting, so that the translocated maternal allele remains active. This study defines one or more gene loci for BWS on 11p15.5 in the genomic region from D11S12 to IGF2.

Beckwith-Wiedemann Syndrome↗
PubMed1991

Localization and genetic linkage of the human immunoglobulin heavy chain genes and the creatine kinase brain (CKB) gene: identification of a hot spot for recombination.

The immunoglobulin heavy chain (IGH) gene cluster and the gene coding for the brain form of the enzyme creatine kinase (CKB) have previously been localized to chromosome 14, at 14q32.3 and 14q32, respectively. Here we report more precise regional localization of these genes by dosage studies using DNA from a child hemizygous for the region from 14q32.32 to 14qter. CKB and IGH are present in a single dose in the proband. Dosage studies in a second patient with a similar but smaller deletion due to a ring chromosome 14 show that CKB is proximal to the IGH cluster. An EcoRI restriction site polymorphism was found with probes for the CKB gene. Linkage analysis of family data indicates that CKB is closely linked to IGH. Linkage analysis also revealed unusually high recombination (beta = 3.2%) between the C delta and C gamma 3 genes of the IGH constant region, which are only 60 kb apart. This finding, in combination with a previous observation of linkage equilibrium in the region, suggests that the C delta-C gamma 3 region contains a recombination hot spot.

Brain↗
PubMed1991

Patients with deletions of 9q22q34 do not define a syndrome: three case reports and a literature review.

Three children with deletions involving the 9q22q34 region are described. A review of clinical features of these three new patients and seven previously reported ones did not demonstrate a recognizable dysmorphic pattern. Our cases illustrate the need for repeat karyotyping at higher levels of resolution when there is a suspicion of a chromosome anomaly, since each deletion was missed on initial analysis.

Abnormalities, Multiple↗
PubMed1990

Echocardiographic evaluation of the spectrum of cardiac anomalies associated with trisomy 13 and trisomy 18.

To investigate the role that cardiac anomalies play in the early death frequently seen in the trisomy 13 and the trisomy 18 syndromes, two-dimensional and Doppler echocardiograms from 31 newborn infants with cytogenetic confirmation of these syndromes seen at one institution over a 4.5 year period (1983 to 1988) were reviewed. The mean age at echocardiography was 1.5 days, and the median age at death was 14 days. Significant cyanosis was present in 58%. Cardiac anomalies that would be considered lethal within the neonatal period were present in only 19% of patients. The most common lesions were atrial septal defect (81%), ventricular septal defect (61%) and patent ductus arteriosus (85%). Most ventricular septal defects and patent ductus arteriosus were large. Valvular dysplasia of one or more valves, graded as mild in most cases, was found in 68%, but was not associated with Doppler evidence of significant regurgitation or stenosis in any subject. Of the four valves, the pulmonary valve, followed by the tricuspid valve, was the most commonly dysplastic. Doppler evidence suggestive of elevated pulmonary artery pressure (low velocity bidirectional flow across the ventricular septal defect and patent ductus arteriosus), although expected, was accompanied by greater than normal mean right ventricular cavity and free wall dimensions in these patients. Thus, although the cardiac anomalies most frequently encountered in trisomy 13 and trisomy 18 are nonlethal, the combined findings of frequent cyanosis and increased right ventricular dimensions suggest that other factors such as pulmonary hypertension, perhaps related to maldevelopment of the pulmonary vasculature, may contribute to early death in some of these infants.

Abnormalities, Multiple↗
PubMed1990

Molecular characterization of Beckwith-Wiedemann syndrome (BWS) patients with partial duplication of chromosome 11p excludes the gene MYOD1 from the BWS region.

The molecular characterization of two patients with features of Beckwith-Wiedemann syndrome (BWS) and chromosome abnormalities is consistent with the association of this phenotype with a duplication of a portion of chromosome 11. Quantitative Southern blot analysis of DNA from patient A defines a large inherited duplicated segment of chromosome 11. For patient B, a de novo duplication of unknown origin has been shown to contain a segment of 11p15. This chromosome segment includes the genes for insulin-like growth factor 2, beta-hemoglobin, calcitonin A (CALCA), and parathyroid hormone (PTH). However, the myogenic differentiation factor, MYOD1, is not included in the duplicated segment. This demonstrates that MYOD1 is proximal to CALCA and PTH and excludes MYOD1 as the BWS gene. These data place the BWS gene distal to MYOD1 on 11p15.

Beckwith-Wiedemann Syndrome↗
PubMed1990

Physical mapping of probes within 14q32, a subtelomeric region showing a high recombination frequency.

The genetic linkage map of chromosome 14q32 contains 11 loci which span a distance of more than 60 cM. We have assigned 10 of these loci and the AKT1 proto-oncogene to segments of 14q32, using breakpoints derived from four independent chromosomal deletions or rearrangements. The most telomeric breakpoint was found in a proband (HSC 6) carrying a ring-14 chromosome. HSC 6 is monosomic for the distal part of 14q32, which contains the immunoglobulin heavy-chain locus (IGH), and random markers D14S20, D14S19, and D14S23. Two other chromosomal breakpoints, found in probands HSC 121 and HSC 981, could not be distinguished from each other using DNA probes, although the cytogenetic breakpoints appeared to be different at 14q32.32 and 14q32.31, respectively. The region between the breakpoints of HSC 6 and HSC 121 contains AKT1, D14S1, D14S17, and D14S16. The entire telomeric band 14q32 is assumed to contain about 10% of chromosome 14, or approximately 10 Mb. The 8 most telomeric loci, including D14S1, map to 14q32.32-qter, which measures only several megabases. However, these loci span a genetic distance of 23 cM. The high recombination frequency contrasts with the observation that two of the gamma genes in the IGH constant region show a high degree of linkage disequilibrium, though 180 kb apart. This finding suggests that a telomeric localization per se does not lead to a higher recombination frequency and favors the hypothesis that the higher recombination frequency at the telomeres may be due to specific "hot spots" for recombination.

Blotting, Southern↗