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J Wauters

Publications and source records attributed to J Wauters.

At least 19 recordsLinked to original sources
PubMed2006

Multiplex ligation-dependent probe amplification to detect subtelomeric rearrangements in routine diagnostics.

Subtelomeric rearrangements are believed to be responsible for 5-7% of idiopathic mental retardation cases. Due to the relative complexity and high cost of the screening methods used till now, only preselected patient populations including mostly the more severely affected cases have been screened. Recently, multiplex ligation-dependent probe amplification (MLPA) has been adapted for use in subtelomeric screening, and we have incorporated this technique into routine diagnostics of our laboratory. Since the evaluation of MLPA as a screening method, we tested 275 unselected patients with idiopathic mental retardation and detected 12 possible subtelomeric aberrations: a der(11)t(11;20)(qter;qter), a 19pter duplication, a der(18)t(18;10)(qter; pter), a 15qter deletion, a 8pter deletion, a 6qter deletion, a der(X)t(X;1)(pter;qter), a der(X)t(X;3)(pter;pter), a 5qter duplication, a 3pter deletion, and two 3qter duplications. The patients can be subdivided into two groups: the first containing de novo rearrangements that are likely related to the clinical presentation of the patient and the second including aberrations also present in one of the parents that may or may not be causative of the mental retardation. In our patient cohort, five (1.8%) subtelomeric rearrangements were de novo, three (1.1%) rearrangements were familial and suggestively disease causing, and four (1.5%) were possible polymorphisms. This high frequency of subtelomeric abnormalities detected in an unselected population warrants further investigation about the feasibility of routine screening for subtelomeric aberrations in mentally retarded patients.

Base Sequence↗
PubMed2005

Congenital diaphragmatic hernia and chromosome 15q26: determination of a candidate region by use of fluorescent in situ hybridization and array-based comparative genomic hybridization.

Congenital diaphragmatic hernia (CDH) has an incidence of 1 in 3,000 births and a high mortality rate (33%-58%). Multifactorial inheritance, teratogenic agents, and genetic abnormalities have all been suggested as possible etiologic factors. To define candidate regions for CDH, we analyzed cytogenetic data collected on 200 CDH cases, of which 7% and 5% showed numerical and structural abnormalities, respectively. This study focused on the most frequent structural anomaly found: a deletion on chromosome 15q. We analyzed material from three of our patients and from four previously published patients with CDH and a 15q deletion. By using array-based comparative genomic hybridization and fluorescent in situ hybridization to determine the boundaries of the deletions and by including data from two individuals with terminal 15q deletions but without CDH, we were able to exclude a substantial portion of the telomeric region from the genetic etiology of this disorder. Moreover, one patient with CDH harbored a small interstitial deletion. Together, these findings allowed us to define a minimal deletion region of approximately 5 Mb at chromosome 15q26.1-26.2. The region contains four known genes, of which two--NR2F2 and CHD2--are particularly intriguing gene candidates for CDH.

Abnormalities, Multiple↗
PubMed2003

Color Doppler imaging is a valuable tool for the diagnosis and management of uterine vascular malformations.

OBJECTIVE: The aim of this study was to assess the spontaneous outcome of uterine vascular malformations detected with ultrasonography and color Doppler, and to investigate the predictive value of color Doppler imaging as to which patients require invasive treatment. METHODS: This was a prospective observational study conducted between January 1999 and February 2001 comprising all consecutive patients diagnosed with a uterine vascular malformation by ultrasonography and color Doppler imaging. Spectral analysis included measurement of flow velocities, pulsatility index (PI) and resistance index (RI). Close follow-up was arranged in all cases and the outcomes were recorded. RESULTS: A total of 30 consecutive patients with uterine vascular malformations were included in the study. Spectral analysis of the vessels in the vascular malformations within the myometrium and endometrium revealed the presence of a low-impedance and high-velocity flow. The average values for PI, RI, peak systolic velocity (PSV) and time-averaged maximum velocity (TAMXV) were 0.50, 0.38, 0.63 m/s and 0.46 m/s, respectively. Eight patients (27%) eventually required embolization of the uterine arteries and three of them had true arteriovenous malformations confirmed at angiography. PSV values of >/= 0.83 m/s were associated with higher probabilities of further treatment, such as an embolization, whereas no vascular malformation with a PSV value < 0.39 m/s required embolization. CONCLUSION: Conservative management is possible in more than two-thirds of patients presenting with uterine vascular malformations diagnosed by color Doppler sonography. Despite considerable overlap, PSV values appear to be useful in distinguishing between low- and high-risk patients.

Adult↗
PubMed2000

Expression profile of telomerase subunits in human pleural mesothelioma.

Using the TRAP assay, telomerase activity was previously detected in over 90% of human pleural mesotheliomas (MMs), but not in mesothelial cell cultures (MCCs), suggesting that telomerase re-activation occurs during multi-step mesothelioma carcinogenesis. The present study determined the expression of the telomerase RNA template (hTERC), the telomerase-associated protein (hTEP1), and the telomerase catalytic sub-unit (hTERT), in 16 pleural MMs and 4 MM-derived cell lines, in two pleural solitary fibrous tumours and in six MCCs. Reverse transcription-polymerase chain reaction analysis revealed that hTERT mRNA expression parallels the activity status documented by the TRAP assay, whereas hTERC and hTEP1 mRNA are commonly expressed in all malignant and non-malignant serosal cells and tissues. Three alternatively spliced hTERT transcripts were detected in all telomerase-positive samples, whereas neither variant could be detected in the MCCs. Detection of the hTERT protein with a commercially available antibody was not successful. These results indicate that hTERT expression is rate-limiting for human telomerase activity and that re-activation, rather than up-regulation, of hTERT expression can play a critical role in MM carcinogenesis. While waiting suitable anti-hTERT antibodies, these results provide information for the design of hTERT mRNA-specific in situ probes to study telomerase in archived pre-malignant serosal lesions.

Blotting, Western↗
PubMed2000

Differentiation-dependent alternative splicing and expression of the extracellular matrix protein 1 gene in human keratinocytes.

The human extracellular matrix protein 1 (Ecm1) gene is located at chromosome band 1q21 close to the epidermal differentiation complex and is transcribed in two discrete mRNAs: a full length Ecm1a and a shorter, alternatively spliced, Ecm1b transcript, the expression of which is restricted to tonsils and skin. The chromosomal localization and the Ecm1b expression in skin prompted us to investigate the role of Ecm1 in keratinocyte differentiation. In this study, we provide evidence for the existence of a relationship between keratinocyte differentiation and expression of the Ecm1b transcript. Cultures of subconfluent undifferentiated normal human keratinocytes express only Ecm1a. Upon reaching confluence, the cells start to differentiate, as measured by keratin K10 mRNA expression. Concomitantly Ecm1b mRNA expression is induced, although expression of Ecm1a mRNA remains unchanged. In addition, treatment of undifferentiated normal human keratinocyte cells with 12-O-tetradecanoyl-phorbol-13-acetate strongly induces the expression of Ecm1b mRNA. Expression of Ecm1b can also be induced by coculturing normal human keratinocytes with lethally irradiated feeder cells and by a diffusible factor secreted by stromal cells. In adult human skin, Ecm1a mRNA is expressed throughout the epidermis with the strongest expression in the basal and first suprabasal cell layers, whereas expression of Ecm1b mRNA is predominantly found in spinous and granular cell layers. Immunohistochemically, Ecm1a expression is almost completely restricted to the basal cell layer, whereas Ecm1b is detected in the suprabasal layers. These results are strongly suggestive of a role for Ecm1b in terminal keratinocyte differentiation, which is also supported by the localization of the Ecm1 gene at 1q21. Refinement of its genomic localization, however, placed Ecm1 centromeric of the epidermal differentiation complex.

Adult↗
PubMed2000

Effects of a novel non-carboxylic thromboxane A2 receptor antagonist (BM-531) derived from torasemide on platelet function.

In this study we examined the thromboxane A(2)(TXA(2)) receptor antagonist property of BM-531 (N-tert -butyl- N'-[(2-cyclohexylamino-5-nitrobenzene)sulfonyl]urea), a torasemide derivative, on platelet function. The drug affinity for human washed platelet TXA(2)receptors labelled with [(3)H]SQ-29,548 has been determined (IC50: 0.0078 microM) and demonstrated to be higher than sulotroban (IC50: 0.93 microM) and SQ-29,548 (IC50: 0.021 microM). The antiaggregatory potency has been confirmed since we demonstrated that BM-531 prevented platelet aggregation in human citrated platelet-rich plasma induced by arachidonic acid (600 microM) (ED100: 0.125 microM), U-46619, a stable TXA(2)agonist (1 microM) (ED50: 0.482 microM) and collagen (1 microg mL(-1)) (% of inhibition: 42.9% at 10 microM) and inhibited the second wave of ADP (2 microM). Moreover, when BM-531 was incubated in whole blood from healthy donors, the closure time measured by the recently developed platelet function analyser (PFA-100(trade mark)) was significantly prolonged. These results suggest that BM-531 can be regarded as a novel non-carboxylic TXA(2)antagonist with a powerful antiplatelet potency.

Adenosine Diphosphate↗
PubMed2000

Familial mental retardation syndrome ATR-16 due to an inherited cryptic subtelomeric translocation, t(3;16)(q29;p13.3).

In the search for genetic causes of mental retardation, we have studied a five-generation family that includes 10 individuals in generations IV and V who are affected with mild-to-moderate mental retardation and mild, nonspecific dysmorphic features. The disease is inherited in a seemingly autosomal dominant fashion with reduced penetrance. The pedigree is unusual because of (1) its size and (2) the fact that individuals with the disease appear only in the last two generations, which is suggestive of anticipation. Standard clinical and laboratory screening protocols and extended cytogenetic analysis, including the use of high-resolution karyotyping and multiplex FISH (M-FISH), could not reveal the cause of the mental retardation. Therefore, a whole-genome scan was performed, by linkage analysis, with microsatellite markers. The phenotype was linked to chromosome 16p13.3, and, unexpectedly, a deletion of a part of 16pter was demonstrated in patients, similar to the deletion observed in patients with ATR-16 syndrome. Subsequent FISH analysis demonstrated that patients inherited a duplication of terminal 3q in addition to the deletion of 16p. FISH analysis of obligate carriers revealed that a balanced translocation between the terminal parts of 16p and 3q segregated in this family. This case reinforces the role of cryptic (cytogenetically invisible) subtelomeric translocations in mental retardation, which is estimated by others to be implicated in 5%-10% of cases.

Abnormalities, Multiple↗
PubMed2000

Herve favre

Explore the source record for details and available documents.

Journal Article↗
PubMed2000

[Should the dentin smear layer be preserved or eliminated? (Review of the literature)].

The smear layer is a direct consequence of instrumentation of the root canal wall. Hand instrumentation as well as ultrasonic instrumentation produce a smear layer on the canal wall. This smear layer is composed of dentine, remnants of pulp tissue and odontoblastic processes and bacteria in an infected canal. Removal of the smear layer is accomplished by the irrigation of root canals with EDTA (17%) followed by NaOCl (5.25%). Permeability of the dentine is increased by the removal of smear layer. In this way the bacteria within the infected tubuli can be more easily destroyed by an intracanal dressing. Whether the removal of smear layer decreases the apical leakage is uncertain. To establish the clinical consequences from removal or preservation of the smear layer, further research is needed.

Bacteria↗
PubMed1999

Genomic organization and chromosomal localization of the Itm2a gene.

Itm2A is a novel type II integral membrane protein that is involved in osteo- and chondrogenic differentiation. Itm2a cDNA was originally isolated from a cDNA library of organ cultures from prenatal mouse mandibular condyles, by subtractive hybridization and differential screening. The Itm2a gene was isolated from a BALB/c liver genomic library. In total, 9.4 kb of the gene were sequenced, of which 2649 bp are 5' flanking sequences. The Itm2a gene contains six exons and five introns. The splice sites conform to the GT/AG rule. The 5' flanking region, which contains the presumed promoter sequence, lacks the common TATAA and CCAAT sequences, but contains consensus binding sites for various transcription factors. Several of these transcription factors are known to play a role in transcriptional regulation of cartilage- or bone-specific genes (e.g. Cbfa1, Cart-1, MHox, HES-1, and CIIS1). Itm2a was mapped to mouse chromosome position XA2-XA3 by fluorescent in situ hybridization (FISH) analysis. The human homolog, ITM2A, was mapped to chromosome position Xq13.3-Xq21.2.

Animals↗
PubMed1999

Molecular and clinical examination of an Italian DEFECT11 family.

The DEFECT11 syndrome is a contiguous gene syndrome associated with deletions in the proximal part of chromosome 11p. In this study, we describe in an Italian family the co-existence of multiple exostoses (EXT) and enlarged parietal foramina (FPP), the two major symptoms of this syndrome, with abnormalities of the central nervous system. The latter may be a yet undescribed feature of DEFECT11 syndrome. FISH and molecular analysis allowed us to identify a small deletion on 11p11-p12, further refining the localisation of the FPP gene involved in the DEFECT11 syndrome.

Adult↗
PubMed1999

A gene for autosomal dominant hearing impairment (DFNA14) maps to a region on chromosome 4p16.3 that does not overlap the DFNA6 locus.

Non-syndromic hearing impairment is one of the most heterogeneous hereditary conditions, with more than 40 reported gene localisations. We have identified a large Dutch family with autosomal dominant non-syndromic sensorineural hearing impairment. In most patients, the onset of hearing impairment is in the first or second decade of life, with a slow decline in the following decades, which stops short of profound deafness. The hearing loss is bilateral, symmetrical, and only affects low and mid frequencies up to 2000 Hz. In view of the phenotypic similarities of this family with an American family that has been linked to chromosome 4p16.3 (DFNA6), we investigated linkage to the DFNA6 region. Lod score calculations confirmed linkage to this region with two point lod scores above 6. However, as haplotype analysis indicated that the genetic defect in this family is located in a 5.6 cM candidate region that does not overlap the DFNA6 region, the new locus has been named DFNA14.

Adolescent↗
PubMed1998

Prenatal diagnosis of a constitutional interstitial deletion of chromosome 5 (q15q31.1) presenting with features of congenital contractural arachnodactyly.

Prenatal diagnosis of a constitutional interstitial deletion of chromosome 5 (q15q31.1) in a 30-year-old woman is reported. At 21 weeks of pregnancy, routine fetal ultrasounds showed the presence of apparently isolated bilateral club feet. Fetal karyotyping documented an interstitial deletion of the long arm of chromosome 5: 46,XX,del(5) (q15q31) in all 50 analyzed metaphases. Because such deletion is associated with severe psychomotor retardation, the pregnancy was terminated. Postmortem karyotyping of skin fibroblasts confirmed the presence of this interstitial de novo deletion in all mitoses. The breakpoints on 5q were analyzed by fluorescent in situ hybridization and were localized at 5q15 and q31.1. This case illustrates the importance of fetal karyotyping in cases of isolated club feet. At autopsy, the fetus presented had minor anomalies and contractures of knee and hip joints. These clinical findings could fit the diagnosis of congenital contractural arachnodactyly (CCA) or Beals syndrome. CCA is caused by a defect in the fibrillin-2 (FBN2) gene. This gene was previously mapped on 5q23-31. Our molecular studies of both parents and the fetus, using an intragenic polymorphic GT repeat, showed that the FBN2 gene was deleted in the fetus and that the de novo interstitial deletion occurred on the paternally inherited chromosome 5. Thus, CCA may be caused by a loss of function of the FBN2 gene. Clinical findings in this fetus and those of other described cases with interstitial 5q deletions are reviewed, and similarities with CCA are stressed.

Abnormalities, Multiple↗
PubMed1998

Identification of a third EXT-like gene (EXTL3) belonging to the EXT gene family.

Two homologous genes, EXT1 and EXT2, responsible for the development of benign multiple cartilagenous bone tumors (exostoses) on the long bones, have been identified in the past 2 years. Several arguments have been provided to support the hypothesis that these genes have tumor suppressor activity and that loss of function of these genes may contribute to the development of bone tumors. The recent identification of two EXT-like genes, EXTL1 and EXTL2, homologous to the EXT genes and to each other, revealed the existence of a larger family of genes. We now report the identification of a homologous EST (EST01365), not derived from the known EXT and EXTL genes, indicating the existence of one additional member of this gene family. We characterized this third EXT-like gene, EXTL3, and compared it with the other four members of the EXT-EXTL family. In view of its putative tumor suppressor function, the EXTL3 gene can be considered a candidate gene for the breast cancer locus on chromosome 8p12-p22.

Blotting, Northern↗
PubMed1997

The human extracellular matrix gene 1 (ECM1): genomic structure, cDNA cloning, expression pattern, and chromosomal localization.

The Ecm1 gene encodes an 85-kDa protein of unknown function that was originally identified as a secretory protein of the murine osteogenic stromal cell line MN7. This paper describes the isolation of a genomic clone containing the human ECM1 gene from a chromosome 1 cosmid library and the characterization of its exon-intron structure. The protein coding region comprises 10 exons. The ECM1 gene maps at chromosome 1q21 outside the epidermal differentiation complex region. The ECM1 gene appears to be expressed as a 1.8-kb transcript predominantly in placenta and heart, while an additional 1.4-kb alternatively spliced message was detected in tonsils. The full-length human ECM1 transcript contains 1838 bp and has an overall homology of 79.6% with the mouse Ecm1 cDNA. This transcript codes for a protein of 540 amino acids that is 69.4% identical and 81.3% similar to the corresponding mouse protein. The alternatively spliced variant, 1450 bp long, encodes a protein of 415 amino acids.

Alternative Splicing↗
PubMed1996

Positional cloning of a gene involved in hereditary multiple exostoses.

Hereditary multiple exostosis (EXT) is an autosomal dominant condition mainly characterized by the presence of multiple exostoses on the long bones. These exostoses are benign cartilaginous tumors (enchondromata). Three different EXT loci on chromosomes 8q (EXT1), 11p (EXT2) and 19p (EXT3) have been reported, and recently the EXT1 gene was identified by positional cloning. To isolate the EXT2 gene, we constructed a contig of yeast artificial chromosomes (YAC) and P1 clones covering the complete EXT2 candidate region on chromosome 11p11-p12. One of the transcribed sequences isolated from this region corresponds to a novel gene with homology to the EXT1 gene, and harbours inactivating mutations in different patients with hereditary multiple exostoses. This indicates that this gene is the EXT2 gene. EXT2 has an open reading frame encoding 718 amino acids with an overall homology of 30.9% with EXT1, suggesting that a family of related genes might be responsible for the development of EXT.

Amino Acid Sequence↗