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Biomedical subjects

M Vekemans

Publications and source records attributed to M Vekemans.

At least 109 records · Page 6Linked to original sources
PubMed1998

Prenatal diagnosis of an 8p23.1 deletion in a fetus with a diaphragmatic hernia and review of the literature.

The prenatal diagnosis of an 8p23.1 deletion is reported. The diagnosis was ascertained at 22 weeks of gestation because of the discovery of a diaphragmatic hernia at ultrasound. Following cytogenetic studies and counselling, the pregnancy was terminated. An autopsy confirmed the presence of a diaphragmatic hernia and revealed also the existence of an atrio-ventricular canal (AVC) and an atrial septal defect (ASD). The clinical features of this antenatally diagnosed case are compared with those observed in 16 previously reported cases with an identical deletion of the short arm of chromosome 8. This suggests that a deletion 8p23.1 should be considered whenever a diaphragmatic hernia and/or an AVC is detected on ultrasound.

Adult↗
PubMed1998

Insulin-like 4 (INSL4) gene expression in human embryonic and trophoblastic tissues.

Polypeptide growth factors play an important role in the regulation of human embryonic development. Insulin-like 4 gene (INSL4) is a member of the insulin family, which includes insulin, IGF-I, IGF-II, relaxin, and INSL3. Using RT-PCR, we previously found abundant INSL4 mRNA in the human placenta. In this study, we examined the chronology and spatial expression of this gene in sections of human placenta and conceptus by means of in situ hybridization. Expression of the IGF-II gene was studied as a positive control. INSL4 distribution was tissue- and cell-specific. Indeed, INSL4 mRNA was most abundant in syncytiotrophoblast cells. In fetal tissues, INSL4 mRNA was identified in the perichondrium of all four limbs, vertebrae, and ribs. Moreover, INSL4 mRNA was abundant in interbone ligaments. These findings indicate that the INSL4 gene may play an important role in trophoblast development and regulation of bone formation. IGF-II mRNA, in agreement with the literature, are mainly located in the mesodermal core in the villous trophoblast and in most embryonic tissues.

Gene Expression Regulation, Developmental↗
PubMed1998

Prevalence of the microdeletion 22q11 in newborn infants with congenital conotruncal cardiac anomalies.

UNLABELLED: Conotruncal malformations account for about 50% of congenital heart defects diagnosed in newborns. We studied prospectively 104 patients admitted in our neonatal intensive care unit for conotruncal defects by fluorescence in situ hybridization to estimate the prevalence of the interstitial deletion in this category of congenital heart disease. Cardiac phenotypes were: truncus arteriosus (17), interrupted aortic arch (18), tetralogy of Fallot with or without pulmonary valve atresia (55), tetralogy of Fallot with absent pulmonary valves (5), ventricular septal defect with malalignment of the conal septum (9). We discovered a microdeletion 22q11 at loci D22S39 or D22S398 in 50 newborns (48%). The prevalence of this microdeletion in different groups of conotruncal defects was: truncus arteriosus 7/17, interrupted aortic arch 16/18, tetralogy of Fallot 19/55, absent pulmonary valves 2/5, and ventricular septal defect 6/9 respectively. Only two patients without any clinical or biological feature of the so called CATCH22 syndrome exhibited the deletion. Parental studies confirmed that the deletion occurred de novo in 47/50 cases (three parental microdeletions). On the other hand, recurrence of conotruncal heart defects in families of "undeleted probands" was higher than expected (13%). CONCLUSION: In 50/104 newborns with conotruncal defects, an interstitial deletion 22q11 was found. Fluorescence in Situ Hybridization should be performed in newborn infants with conotruncal defect and at least one additional manifestation of the CATCH22 phenotype.

Chromosome Deletion↗
PubMed1998

Spatio-temporal expression of FGFR 1, 2 and 3 genes during human embryo-fetal ossification.

Mutations in FGFR 1-3 genes account for various human craniosynostosis syndromes, while dwarfism syndromes have been ascribed exclusively to FGFR 3 mutations. However, the exact role of FGFR 1-3 genes in human skeletal development is not understood. Here we describe the expression pattern of FGFR 1-3 genes during human embryonic and fetal endochondral and membranous ossification. In the limb bud, FGFR 1 and FGFR 2 are initially expressed in the mesenchyme and in epidermal cells, respectively, but FGFR 3 is undetectable. At later stages, FGFR 2 appears as the first marker of prechondrogenic condensations. In the growing long bones, FGFR 1 and FGFR 2 transcripts are restricted to the perichondrium and periosteum, while FGFR 3 is mainly expressed in mature chondrocytes of the cartilage growth plate. Marked FGFR 2 expression is also observed in the periarticular cartilage. Finally, membranous ossification of the skull vault is characterized by co-expression of the FGFR 1-3 genes in preosteoblasts and osteoblasts. In summary, the simultaneous expression of FGFR 1-3 genes in cranial sutures might explain their involvement in craniosynostosis syndromes, whereas the specific expression of FGFR 3 in chondrocytes does correlate with the involvement of FGFR 3 mutations in inherited defective growth of human long bones.

Bone and Bones↗
PubMed1998

SHOX mutations in dyschondrosteosis (Leri-Weill syndrome).

Dyschondrosteosis (DCS) is an autosomal dominant form of mesomelic dysplasia with deformity of the forearm (Madelung deformity; ref. 3). Based on the observation of XY translocations (p22,q12; refs 4-6) in DCS patients, we tested the pseudoautosomal region in eight families with DCS and showed linkage of the DCS gene to a microsatellite DNA marker at the DXYS233 locus (Zmax=6.26 at theta=0). The short stature homeobox-containing gene (SHOX), involved in idiopathic growth retardation and possibly Turner short stature, maps to this region and was therefore regarded as a strong candidate gene in DCS. Here, we report large-scale deletions (in seven families) and a nonsense mutation (in one family) of SHOX in patients with DCS and show that Langer mesomelic dwarfism results from homozygous mutations at the DCS locus.

Female↗
PubMed1998

Genetic analysis of splenic lymphoma with villous lymphocytes: a Groupe Français d'Hématologie Cellulaire (GFHC) study.

In order to characterize the genetic diversity in splenic lymphoma with villous lymphocytes (SLVL), we have undertaken cytogenetic and molecular analyses of CCND1 expression and BCL1-IgH PCR rearrangement in 76 cases diagnosed predominantly on morphological criteria. Cytogenetic abnormalities were detected in 19/44 (43%) of cases, including in 16/25 (64%) of cases with an absolute lymphocytosis. Abnormalities included those involving chromosome 14q32 (9/19, 47%), predominantly t(11;14)(q13;q32) (5/19, 26%), chromosome 3 (26%), predominantly 3q, chromosome 17p (26%) and trisomy 12 (3/19, 16%) and were thus suggestive of pathogenetic diversity. CCND1 was expressed in 8/30 (27%) cases, including in all t(11;14) cases, 5/10 (50%) CD5-positive cases and also in 3/20 (15%) CD5-negative cases. Three CCND1-positive SLVL demonstrated immunophenotypic features similar to mantle cell lymphoma (MCL) but the majority differed in their CD5 negativity or CD23 positivity. BCL1-IgH rearrangement was only seen in 1/62 (2%) of cases overall and in none of the t(11;14) cases, which demonstrated FISH breakpoints both centromeric and telomeric to the BCL1/MTC, suggesting that, if genomic clustering exists in t(11;14) SLVL, it differs from MCL. Although CCND1 expressing SLVL more commonly had marked lymphocytosis, they did not demonstrate a more aggressive clinical course than their negative counterparts, demonstrating that the detection of CCND1 expression or of a t(11;14) should not suffice to alter diagnostic classification in the absence of other criteria.

Aged↗
PubMed1998

FISH detection of chromosome 14q32/IgH translocations: evaluation in follicular lymphoma.

A FISH strategy capable of detecting chromosome 14q32 rearrangements involving the IgH locus, including in interphase nuclei, was developed using Ig variable and constant region cosmids from the extremities of the locus in a dual hybridization approach, using signal splitting as evidence of rearrangement. The large size of the locus (1.3 Mb) and the propensity for internal deletion due to physiological VDJ recombination and isotype switching complicate analysis of this locus. We used the Ig10 cosmid, which hybridizes to C epsilon and C alpha2 at the 3' end of the constant region, in order to minimize deletion and/or splitting of the constant region probe. Cos Ig10 and the IgV18 VH probes were compared with a specific IgH-BCL2 FISH dual hybridization approach in follicular lymphoma (FL). Both were capable of detecting the t(14;18) in interphase nuclei, including in cases with no apparent abnormality by classic karyotype analysis, although the sensitivity of the IgH approach was slightly lower. We have also successfully applied these probes to whole cell cytospin preparations, rendering analysis of cryopreserved material possible, although interpretation should be limited to frequent events, particularly following cell manipulation. Analysis of flow cytometric sorted bone marrow fractions from three FL patients by FISH and FICTION showed that the t(14;18) was present in a much lower proportion of CD34 positive than negative cells but that the higher level of background hybridization limits use of these techniques for the reliable quantification of rare events.

Cell Separation↗
PubMed1998

Wilms' tumor and gonadal dysgenesis in a child with the 2q37.1 deletion syndrome.

Here we report Wilms' tumor, gonadal dysgenesis and a bifid uterus in an 18-month-old female with a terminal deletion of the long arm of chromosome 2 [46,XX,del(2)(q37.1)]. Since Wilms' tumor has been previously reported in the 2q37 deletion syndrome, the present observation raises the question of whether a tumor susceptibility gene maps to chromosome 2q37 and suggests giving consideration to the possible occurrence of Wilms' tumor in the course of disease.

Abnormalities, Multiple↗
PubMed1998

Incidence of sex chromosome abnormalities in spermatozoa from patients entering an IVF or ICSI protocol.

OBJECTIVE: The objective of this study was the determination of sex chromosome aneuploidy frequency in spermatozoa from patients included in an in vitro fertilization (IVF) or intra cytoplasmic sperm injection (ICSI) protocol. METHODS: Spermatozoa from nineteen patients, including patients with normal seminal parameters according to World Health Organization (WHO) criteria and patients exhibiting abnormal seminal parameters, were analyzed by dual color fluorescence in situ hybridization (FISH) for aneuploidies of the X and Y chromosomes. Our technique, using only probes for sex chromosomes and not for autosomes, does not discriminate between hyperhaploid and diploid sperm nuclei. The results were analyzed in two different ways: in relation to the semen status, denoted normal or abnormal and with regard to the ability of the sperm to fertilize oocytes when IVF or ICSI was performed. RESULTS: Abnormal semen showed a significant increase in the overall rate of sperm nuclei with XY, XX and YY sex chromosome complements, 1.59% compared to normal semen, 0.78% (p<0.02). Semen shown to be able to fertilize oocytes only by ICSI showed a higher incidence of XY-bearing spermatozoa, 1.26%, compared to semen able to fertilize oocytes by conventional IVF, 0.37% (p<0.001). The incidence of XX-or YY-bearing sperm nuclei was also significantly elevated in the ICSI group (0.25% XX, 0.50% YY) (p<0.02) as compared to the IVF group (0.06% XX, 0.16% YY). CONCLUSIONS: We concluded that infertile men requiring ICSI treatment showed a higher incidence of sex chromosome aneuploidy, due to meiosis I and II nondisjunction, in their spermatozoa as compared to men requiring IVF for reasons of predominantly female infertility.

Aneuploidy↗
PubMed1998

Simultaneous detection of MYC, BVR1, and PVT1 translocations in lymphoid malignancies by fluorescence in situ hybridization.

The rapid detection of chromosome band 8q24 rearrangements, including classical translocations involving MYC and variant 3' translocations, is important for the accurate diagnosis and appropriate treatment of lymphoid malignancies. We have identified and characterized a CEPH YAC, 934e1, which extends from at least 190 kbp upstream to over 280 kbp downstream to MYC, allowing detection of classical t(8; 14)(q24;q32) and variant t(8;22)(q24;q11) and t(8;14)(q24;q11), extending distal to PVT1 and therefore, by extrapolation, to BVR1. This YAC also allowed clarification of complex chromosome 8 abnormalities and the identification of translocations in interphase nuclei. A second CEPH YAC, 904c3, previously shown to contain the PVT1 locus but not MYC, allowed distinction between translocations occurring centromeric and telomeric to MYC. Use of the 934e1 YAC will aid classification of a variety of lymphoid proliferations and further characterization of rearranged cases with the 904c3 YAC will simplify mapping of their diverse breakpoints.

Chromosomes, Artificial, Yeast↗
PubMed1998

[Recent progress in contraception].

The main new opportunities in contraceptive technology are the monofilament intra-uterine device (IUD) loaded with copper cylinders, the levonorgestrel-releasing IUD, the subcutaneous implants releasing the same hormone and the possibility of drug-induced medical abortion. Recent research concerning vascular complications related to oral contraception, especially with the third generation progestagens, rises interesting but still unresolved questions because of the numerous bias prevailing in case-control studies. Until now, there is no consensus about new prescription attitudes in relation with the risk of such vascular events. Low-dosis pills (oestrogen at 20 micrograms) are not a first choice for oral contraception as they often induce spotting and abnormal blood loss, and therefore entail low compliance. The contraceptive effects of (quasi-) exclusive breast feeding have been figured out and have resulted in the Lactational Amenorrhoea Method (LAM). Future contraceptive methods will include new postcoïtal methods, new injectables with quicker reversibility and less amenorrhoea, biodegradable implants, weekly applicable patches, male-oriented methods combining an androgen and a progestin, and reversible immuno-contraception directed against the gonadotropins.

Bias↗
PubMed1997

A chromosome 14q11/TCR alpha/delta specific yeast artificial chromosome improves the detection rate and characterization of chromosome abnormalities in T-lymphoproliferative disorders.

The rate of detection of chromosome abnormalities in T-cell proliferations is lower than that observed in B-cell malignancies. The former frequently involve the TCR alpha/delta locus at chromosome band 14q11. We have identified a YAC encompassing 70% of the TCR alpha/delta locus, which has been used as a fluorescence in situ hybridization probe to detect chromosome rearrangements involving 14q11, both at metaphase and within interphase nuclei, in patients with a variety of T-lymphoproliferative disorders. Its use allowed detection of previously unsuspected TCR alpha/delta rearrangements in 4/13 (30%) immature T-lineage acute leukemias, including two t(10;14) and 2 minor inversion 14s. It also clarified interpretation of complex chromosome 14 abnormalities in mature T-cell proliferations (T-prolymphocytic leukemia and ataxia telangiectasia). Use of this probe will aid the detection and characterization of abnormalities involving the TCR alpha/delta locus, particularly in cases with normal or complex karyotypes and in those proliferations for which mitoses are difficult to obtain.

Chromosome Aberrations↗
PubMed1997

Prezygotic origin of the isochromosome 12p in Pallister-Killian syndrome.

Pallister-Killian syndrome is a rare disorder comprising multiple congenital anomalies, streaks of hypo(hyper)pigmentation, seizures, profound mental retardation, and the presence of an extra metacentric chromosome i(12)(p10), usually limited to skin fibroblasts. The mechanism and parental origin of the extra chromosome i(12)(p10) are unknown. Here, we present a girl with Pallister-Killian syndrome and the i(12)(p10) in 50% of cultured skin fibroblasts. Using microsatellite DNA markers of chromosome 12p, we detected 3 alleles--including 2 different alleles of maternal origin--in cultured skin fibroblasts, suggesting that the tetrasomy 12p is the result of a prezygotic event, with a nondisjunction event during maternal meiosis.

Abnormalities, Multiple↗
PubMed1997

Continuation rates with a levonorgestrel-releasing contraceptive implant (Norplant). A prospective study in Belgium.

Contraceptive protection offered by a method depends on its duration of use, which reflects costs, side effects, and relatives' opinions. This study investigated in Norplant implants users the continuation rates, some of their determinants, and the motives for removals. Since 1988, 612 Norplant implants sets, designed to protect for 5 years, have been inserted. Observing 13,907 months of use, we determined over time the continuation rates and how age, parity, circumstances at insertion (postpartum, postabortum, others), and patronymic origins (surrogate for sociocultural factors) influenced them. Statistics included Kaplan-Meier's method and log rank tests, and uni- and multivariate Cox models. Continuation increased with age and depended on sociocultural factors. Parity exerted influence only in younger women. Median duration of use was 3 years 11 months. Removals before 5 years related almost equally to irregular bleeding, other side effects, and pregnancy wish. The cumulative 5-year failure rate was 1.5%. Unsatisfied users returned earlier, distorting the first results. A literature search showed that implants yield, in the mean, slightly better continuation figures than do intrauterine devices, and clearly higher than those obtained with pills and injectables. To optimize costs and counseling, warnings about the risk of short duration of use in young nullipara, especially if negative sociocultural influences prevail, are recommended. In no category are the implants absolutely to be avoided. Individual and programmatic contraceptive choice should take into account the expected continuation of use.

Adolescent↗
PubMed1997

Abnormal FGFR 3 expression in cartilage of thanatophoric dysplasia fetuses.

Thanatophoric dysplasia (TD), the commonest lethal skeletal dysplasia in humans, is accounted for by recurrent mutations in the fibroblast growth factor receptor 3 gene (FGFR 3), causing its constitutive activation in vitro. Taking advantage of medical abortion of 18 TD fetuses, cartilage sections were studied for FGFR 3 gene expression by in situ hybridization and immunohistochemistry. Specific antibodies revealed high amounts of FGFR 3 in cartilage of TD fetuses with no increased level of the corresponding mRNA. The specific signal was mainly detected in the nucleus of proliferative and hypertrophic chondrocytes. Based on this observation and the abnormal expression of collagen type X in hypertrophic TD chondrocytes, we suggest that constitutive activation of the receptor through formation of a stable dimer increases its stability and promotes its translocation into the nucleus, where it might interfere with terminal chondrocyte differentiation.

Cartilage↗
PubMed1997

Features of DiGeorge syndrome and CHARGE association in five patients.

We report on five patients presenting with features of two congenital disorders, DiGeorge syndrome (DGS) and CHARGE association. CHARGE association is usually sporadic and its origin is as yet unknown. Conversely, more than 90% of DGS patients are monosomic for the 22q11.2 chromosomal region. In each of the five patients, both cytogenetic and molecular analysis for the 22q11.2 region were normal. In view of the broad clinical spectrum and the likely genetic heterogeneity of both disorders, these cases are consistent with the extended phenotype of either DGS without 22q11.2 deletion or CHARGE association, especially as several features of CHARGE association have been reported in rare patients with 22q11.2 deletion association phenotypes. On the other hand, these could be novel cases of an independent association involving a complex defect of neural crest cells originating from the pharyngeal pouches.

Abnormalities, Multiple↗
PubMed1997

Interstitial duplication of the short arm of chromosome 2: report of a new case and review.

An 18 month old girl was referred to us because of dysmorphic features and psychomotor and growth retardation. On physical examination, she was found to have microcephaly, open fontanelles, a prominent forehead, a flat occiput, hypertelorism, sparse eyebrows, a small nose with a depressed nasal bridge, a bulging philtrum, a thin upper lip, a high arched palate, low set and posteriorly rotated ears, a small mandible, a short neck with a low hair line, and eye malformations. High resolution chromosome analysis identified a de novo direct duplication of the 2p21.00-->p24.2 region. The phenotype of de novo partial trisomy 2p is discussed.

Adult↗