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Sylvie Langlois

Publications and source records attributed to Sylvie Langlois.

18 recordsLinked to original sources
PubMed2006

Identification of transcripts modulated by ETV6 expression.

Deletions at chromosome 12p12-13 are observed in 26-47% of childhood pre-B acute lymphoblastic leukaemia (ALL) cases, suggesting the presence of a tumour suppressor gene (TSG). Accumulating genetic and functional evidence points to ETV6 as being the most probable TSG targeted by the deletions. ETV6 is a ubiquitously expressed transcription factor of the ETS family with very few known targets. To understand its function and to elucidate the impact of its absence in leukaemia, we conducted a study to identify targeted genes. Following the induction of ETV6 expression, global expression was evaluated at different time points. We identified 87 modulated genes, of which 10 (AKR1C1, AKR1C3, IL18, LUM, PHLDA1, PTGER4, PTGS2, SPHK1, TP53 and VEGF) were validated by real-time quantitative reverse transcription-polymerase chain reaction. To assess the significance of the validated candidate genes in leukaemia, their expression patterns were determined, as well as that of ETV6, in pre-B ALL patients. The expression of IL18, LUM, PTGER4, SPHK1 and TP53 was significantly correlated with that of ETV6, further suggesting that ETV6 could regulate the expression of these genes in leukaemia. This work constitutes another step towards the understanding of the functions of ETV6 and the impact of its inactivation in childhood leukaemia.

Animals↗
PubMed2006

Oligonucleotide microarray analysis of genomic imbalance in children with mental retardation.

The cause of mental retardation in one-third to one-half of all affected individuals is unknown. Microscopically detectable chromosomal abnormalities are the most frequently recognized cause, but gain or loss of chromosomal segments that are too small to be seen by conventional cytogenetic analysis has been found to be another important cause. Array-based methods offer a practical means of performing a high-resolution survey of the entire genome for submicroscopic copy-number variants. We studied 100 children with idiopathic mental retardation and normal results of standard chromosomal analysis, by use of whole-genome sampling analysis with Affymetrix GeneChip Human Mapping 100K arrays. We found de novo deletions as small as 178 kb in eight cases, de novo duplications as small as 1.1 Mb in two cases, and unsuspected mosaic trisomy 9 in another case. This technology can detect at least twice as many potentially pathogenic de novo copy-number variants as conventional cytogenetic analysis can in people with mental retardation.

Child↗
PubMed2006

Detection and characterization of DNA variants in the promoter regions of hundreds of human disease candidate genes.

Understanding genetic variation might reveal the cause of individual susceptibility to a variety of complex diseases such as asthma, diabetes, and cancer. Current efforts to identify functional DNA variants have essentially been oriented toward single nucleotide polymorphisms (SNPs) found in coding regions of candidate genes since they have direct impact on the structure and function of the affected proteins. Abnormal expression of finely regulated genes could also lead to disequilibria in different metabolic pathways and/or biological processes. Thus investigation of SNPs in the promoter regions (pSNPs) of genes should improve our knowledge of the etiology of complex diseases. Unfortunately, little is known about the nature and the prevalence of pSNPs. We have analyzed 197 genes targeting the promoter region, arbitrarily defined as a 2-kb genomic segment upstream of the transcription initiation site, by screening by dHPLC for the presence of SNPs in a worldwide panel of 40 individuals. As a result 1838 pSNPs were detected, 75% of which modify (by either gain or loss) putative binding sites of known transcription factors. We also examined the distribution of these pSNPs among features such as conserved regions, repeats, and dinucleotides as well as Gene Ontology terms. This report supports the functional relevance of several of the pSNPs investigated and suggests a putative impact on disease susceptibility.

Binding Sites↗
PubMed2006

Postnatal follow-up of prenatally diagnosed trisomy 16 mosaicism.

OBJECTIVE: To determine the long-term outcome of pregnancies prenatally diagnosed with trisomy 16 and identify variables associated with the outcome. METHODS: We reviewed all published and our unpublished data from trisomy 16 pregnancies for which outcomes were available for children of greater than 1 year of age. RESULTS: Nineteen cases were diagnosed with trisomy 16 on chorionic villus sampling (CVS) and 17 cases at amniocentesis. Age at last follow-up ranges from 1 to 13 years. Among the CVS group, four out of five patients, with a birth weight and/or length below -2 SD and postnatal growth information, showed catch-up growth (80%). Among the amniotic fluid (AF) group, the birth weight was available in 13 cases. Eleven of the 13 cases had a birth weight less than -2 SD. In eight cases, the length was also below -2 SD (length data unavailable in one case). Nine out of ten cases (90%) and seven out of eight (87.5%) showed catch-up growth for weight and length, respectively. In terms of development, no cases of CVS mosaicism had global developmental delay. One child had a history of delay in speech development. Among the AF-detected cases, 4/17 cases had global developmental delay. All four children with global developmental delay had more than one major malformation compared to 6 out of 32 children in the group with normal development (p = 0.004). The finding of uniparental disomy (UPD) was not associated with developmental delay. CONCLUSIONS: The majority of prenatally diagnosed trisomy 16 mosaic cases have a good postnatal outcome. However, the finding of mosaicism on AF and the presence of major congenital anomalies are associated with an increased risk of developmental delay.

Amniocentesis↗
PubMed2006

The association between preeclampsia and placental trisomy 16 mosaicism.

BACKGROUND: Prenatally diagnosed trisomy 16 mosaicism is associated with the increased risk of poor pregnancy outcome including intrauterine growth restriction, intrauterine death and fetal malformation. While maternal preeclampsia has also been reported in some cases, this has not been systematically evaluated. METHODS: To better define the risk of preeclampsia and the clinical course of preeclampsia in these pregnancies and to identify associated clinical variables, we reviewed 25 cases of prenatally diagnosed trisomy 16 mosaicism for which molecular studies were undertaken and sufficient obstetrical data were present to include/exclude the diagnosis of preeclampsia. RESULTS: Six of 25 (24%) mosaic trisomy 16 cases exhibited preeclampsia as compared to 3 of 44 (7%) matched controls. There were no differences between those mosaic trisomy 16 cases presenting with preeclampsia and those that did not, in terms of the presence/absence of UPD, IUGR, malformation, or trisomy on amniocentesis. Four of the 6 (67%) preeclampsia-associated fetuses were male, compared with only 4 of 19 (21%) (p = 0.06) nonpreeclampsia case fetuses, and three of these also had hypospadias. The levels of trisomy tended to be high in placentas associated with preeclampsia; however very high levels of placental trisomy were also often seen in the absence of preeclampsia. CONCLUSION: As it is impossible to predict which subset of cases is at highest risk, all women receiving a prenatal diagnosis of trisomy 16 mosaicism should be closely monitored for signs of preeclampsia.

Adult↗
PubMed2006

The impact of prenatal diagnosis on neural tube defect (NTD) pregnancy versus birth incidence in British Columbia.

The birth incidence of neural tube defect (NTD) cases in British Columbia (B.C.), and elsewhere in North America, is reported to be declining. This decline is being attributed to folic acid (FA) supplementation and food fortification, but 2nd trimester prenatal screening of pregnancies for NTDs and other congenital anomalies has increased during this timeframe, as well. This descriptive, population-based study evaluates the impact of prenatal screening of NTD-affected pregnancies on (1) pregnancy outcome and (2) reporting of NTD births to the provincial Health Status Registry (B.C.H.S.R.); and it assesses (3) the use of periconceptional FA supplementation. NTD cases were ascertained from medical records of health centres providing care to families with NTD-affected pregnancies and newborns; and from NTD cases reported to the B.C.H.S.R. In 1997-1999, the B.C.H.S.R. published a NTD incidence of 0.77/1000. In this study, 151 NTD-affected pregnancies were identified, with an incidence of 1.16/1000. Partial Reporting of induced abortions in a NTD incidence 45.5% low than the actual incidence. Medical records were available for review on 144/151 pregnancies. Prenatal screening identified 86.1% (124/144) of NTD-affected pregnancies, with 72.6% (90/124) resulting in pregnancy termination, and 27.4% (34/124) continuing to term. Use of FA supplementation in the periconceptional period was recorded in 36.4% of pregnancies (39/107). Thus in B.C. the decline in the NTD incidence is due predominantly to pregnancy terminations following prenatal diagnosis, which reduces the NTD incidence by 60%, from 1.16/1000 to 0.47/1000. Continued efforts for primary and the option of secondary prevention of NTDs are recommended in order to improve newborn health in B.C. and elsewhere. These interventions need to be monitored, however, for optimal health care planning.

Abortion, Eugenic↗
PubMed2004

Long-term follow-up of three individuals with Kabuki syndrome.

Long-term follow-up of three individuals with Kabuki syndrome indicates their phenotype becomes less striking as adults. It is characterized by short stature, obesity, and relatively large head. Long palpebral fissures persist, as does mild to moderate mental retardation. Independent daily living skills are achieved but a sheltered living environment is needed.

Abnormalities, Multiple↗
PubMed2003

Familial cryptic translocation (2;17) ascertained through recurrent spontaneous abortions.

We report a young woman who presented with a reproductive history of three recurrent spontaneous abortions (RSA) and two neonatal deaths. Comparative genomic hybridization (CGH) was used to determine the chromosomal composition of the patient's last miscarriage. It showed the presence of monosomy for the distal end of chromosome 2 long arm (segment 2q37.2 to qter) and trisomy for the distal end of chromosome 17 long arm (segment 17q25 to qter). The mother was found to be a carrier for a cryptic translocation between chromosomes 2 and 17 long arms by fluorescence in situ hybridization using a subtelomeric probe for 17q. Retrospective CGH analysis on one baby who died neonatally showed that he had inherited the maternal translocation in the same unbalanced state as the last pregnancy loss. His detailed postmortem examination is reported.

Abortion, Habitual↗
PubMed2003

X chromosome inactivation patterns in Russell-Silver syndrome patients and their mothers.

Russell-Silver syndrome (RSS) is a disorder characterized by pre- and post-natal growth deficiency, triangular facies, relative macrocephaly, and body asymmetry. Maternal uniparental disomy for chromosome 7 has been found in approximately 10% of RSS cases, while the cause in the remaining cases is unknown. Although most cases of RSS are sporadic, at least 25 families have been reported with familial RSS and inheritance patterns of RSS consistent with an X-linked dominant mutation. Thus, we hypothesized that skewed X-chromosome inactivation (XCI) could be increased in some females with RSS as a consequence of a tendency to have the mutant allele on the predominantly active chromosome. Alternatively, unaffected mothers of children with RSS may tend to be skewed due to preferential inactivation of the mutant allele. In support of this last hypothesis, a significant increase in extremely skewed XCI (>95%) was found in mothers of children with RSS (4 of 21, 19%) compared to controls (2 of 101, 2%) (P = 0.008). However, an increase in skewed XCI was also observed in female patients who had unexplained short stature but did not fulfill the criteria for RSS (3 of 17, 18%) (P = 0.02), but not in those diagnosed as RSS (0 of 7, n.s.). Different mechanisms may underlie the increase in skewing in each group, possibly being due to different X-linked mutations or growth restriction during very early in utero development.

Abnormalities, Multiple↗
PubMed2002

Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: identification of a novel TfR2 mutation.

Hereditary hemochromatosis (HH) is classically associated with a Cys282Tyr (C282Y) mutation of the HFE gene. Non-C282Y HH is a heterogeneous group accounting for 15% of HH in Northern Europe. Pathogenic mutations of the transferrin receptor 2 (TfR2) gene have been identified in 4 Italian pedigrees with the latter syndrome. The goal of this study was to perform a mutational analysis of the TfR2 and HFE genes in a cohort of non-C282Y iron overload patients of mixed ethnic backgrounds. Several sequence variants were identified within the TfR2 gene, including a homozygous missense change in exon 17, c2069 A-->C, which changes a glutamine to a proline residue at position 690. This putative mutation was found in a severely affected Portuguese man and 2 family members with the same genotype. In summary, pathologic TfR2 mutations are present outside of Italy, accounting for a small proportion of non-C282Y HH.

Canada↗
PubMed2002

Origin of amnion and implications for evaluation of the fetal genotype in cases of mosaicism.

OBJECTIVE: To investigate presence of trisomy in amniotic epithelium (uncultured amnion) and mesenchyme (cultured amnion) from mosaic cases to understand the origins of these tissues and their relationship to pregnancy outcome. METHODS: Polymerase chain reaction (PCR) of microsatellite loci was used to determine the presence of trisomy (of meiotic origin only) in amnion samples from 33 placentas previously ascertained because of a prenatal diagnosis of trisomy mosaicism that was predominantly confined to the placental tissues. RESULTS: In 16 (48%) of 33 cases, trisomy was confirmed to be present by molecular analysis of uncultured amnion. In contrast, cytogenetic analysis of cultured amnion showed trisomy in only 2 of 20 informative cases. The molecular detection of trisomy in amnion was strongly associated with poor pregnancy outcome (intrauterine growth restriction, fetal anomalies and/or intrauterine/neonatal death) even when analysis was limited to cases negative for the trisomy on amniotic fluid (N = 22, p = 0.0005). CONCLUSIONS: We infer that amniotic mesenchyme (usually diploid) derives from early embryonic mesoderm of the primitive streak and not from the hypoblast as is commonly cited. Trisomy in amniotic epithelium suggests that high numbers of abnormal cells were present in the epiblast, and this correlates with poor outcome even when the subsequently derived fetus and amniotic mesenchyme appear to carry only diploid cells.

Abnormalities, Multiple↗
PubMed2002

Dispermy--origin of diandric triploidy: brief communication.

Triploidy may arise from either digynic or diandric fertilizations. Errors in the second meiotic division account for most digynic triploidy while most studies have found that approximately 2/3 of diandric triploids arise as the result of dispermy and 1/3 as the result of meiotic errors giving rise to diploid sperm. Using molecular markers very close to the centromere, all 14 cases of diandric triploidy were shown to be the result of dispermy with no evidence to support a meiotic error as the origin of diandric triploids.

Centromere↗