Molecular detection of single nucleotide polymorphisms on whole blood without DNA extraction
; BOEMER, François ; SEGERS, Karin et al
Poster (2016, May 12)
Breast cancer in a male to female transsexual patient with a BRCA2 mutation
CORMAN, Vinciane ; Potorac, Iulia ; Manto, Florence et al
in Endocrine-Related Cancer (2016)Detailed reference viewed: 24 (6 ULg)
BRCA1 germline mutation and glioblastoma development: report of cases
Boukerroucha, Meriem ; Josse, Claire ; SEGERS, Karin et al
in BMC Cancer (2015), 15
Background Germline mutations in breast cancer susceptibility gene 1 (BRCA1) increase the risk of breast and ovarian cancers. However, no association between BRCA1 germline mutation and glioblastoma ... [more ▼]
Background Germline mutations in breast cancer susceptibility gene 1 (BRCA1) increase the risk of breast and ovarian cancers. However, no association between BRCA1 germline mutation and glioblastoma malignancy has ever been highlighted. Here we report two cases of BRCA1 mutated patients who developed a glioblastoma (GBM). Cases presentation Two patients diagnosed with triple negative breast cancer (TNBC) were screened for BRCA1 germline mutation. They both carried a pathogenic mutation introducing a premature STOP codon in the exon 11 of the BRCA1 gene. Few years later, both patients developed a glioblastoma and a second breast cancer. In an attempt to clarify the role played by a mutated BRCA1 allele in the GBM development, we investigated the BRCA1 mRNA and protein expression in breast and glioblastoma tumours for both patients. The promoter methylation status of this gene was also tested by methylation specific PCR as BRCA1 expression is also known to be lost by this mechanism in some sporadic breast cancers. Conclusion Our data show that BRCA1 expression is maintained in glioblastoma at the protein and the mRNA levels, suggesting that loss of heterozygosity (LOH) did not occur in these cases. The protein expression is tenfold higher in the glioblastoma of patient 1 than in her first breast carcinoma, and twice higher in patient 2. In agreement with the high protein expression level in the GBM, BRCA1 promoter methylation was not observed in these tumours. In these two cases, despite of a BRCA1 pathogenic germline mutation, the tumour-suppressor protein expression is maintained in GBM, suggesting that the BRCA1 mutation is not instrumental for the GBM development. [less ▲]Detailed reference viewed: 35 (6 ULg)
From Sanger to NGS : a rapid, cheap, easy and efficient move to next generation sequencing
SEGERS, Karin ; BYNENS, Amaury ; Bours, Vincent
Poster (2015, March 06)Detailed reference viewed: 27 (6 ULg)
PHARMACOGENOMIQUE ET MEDECINE PERSONNALISEE : VERS UN SCREENING SYSTEMATIQUE DE LA POPULATION ?
DIDEBERG, Vinciane ; SEGERS, Karin ; KOOPMANSCH, Benjamin et al
in Revue medicale de Liege (2015), 70(5-6), 251-6
Recent advances in medical genomics open new perspectives for personalized medicine through the identification of genetic variants that influence drug response and/or the risk of side effects. Today, the ... [more ▼]
Recent advances in medical genomics open new perspectives for personalized medicine through the identification of genetic variants that influence drug response and/or the risk of side effects. Today, the clinical applications of pharmacogenetics remain scarce as a consequence of the cost and turn-around-time of genetic tests. However, a few tests are recommended, for instance before the prescription of some anti-cancer agents or the anti-retroviral agent abacavir. In the future, we will probably move either towards rapid targeted tests or towards a large screening, before any diagnosis, of all the genetic factors influencing the therapeutic response. In that case, physicians will have to consult the patient genomic data before drug prescription in order to personalize the choice of the therapeutic agent or its dosage. However, such a genomic approach brings economical and ethical questions and will require further progress in our capacity to interpret and store the personal genomic data without compromising their confidentiality. [less ▲]Detailed reference viewed: 17 (0 ULg)
Evaluation of BRCA1-related molecular features and microRNAs as prognostic factors for triple negative breast cancers.
Boukerroucha, Meriem ; Josse, Claire ; El Guendi, Sonia et al
in BMC cancer (2015), 15(1), 755
BACKGROUND: The BRCA1 gene plays a key role in triple negative breast cancers (TNBCs), in which its expression can be lost by multiple mechanisms: germinal mutation followed by deletion of the second ... [more ▼]
BACKGROUND: The BRCA1 gene plays a key role in triple negative breast cancers (TNBCs), in which its expression can be lost by multiple mechanisms: germinal mutation followed by deletion of the second allele; negative regulation by promoter methylation; or miRNA-mediated silencing. This study aimed to establish a correlation among the BRCA1-related molecular parameters, tumor characteristics and clinical follow-up of patients to find new prognostic factors. METHODS: BRCA1 protein and mRNA expression was quantified in situ in the TNBCs of 69 patients. BRCA1 promoter methylation status was checked, as well as cytokeratin 5/6 expression. Maintenance of expressed BRCA1 protein interaction with BARD1 was quantified, as a marker of BRCA1 functionality, and the tumor expression profiles of 27 microRNAs were determined. RESULTS: miR-548c-5p was emphasized as a new independent prognostic factor in TNBC. A combination of the tumoral expression of miR-548c and three other known prognostic parameters (tumor size, lymph node invasion and CK 5/6 expression status) allowed for relapse prediction by logistic regression with an area under the curve (AUC) = 0.96. BRCA1 mRNA and protein in situ expression, as well as the amount of BRCA1 ligated to BARD1 in the tumor, lacked any associations with patient outcomes, likely due to high intratumoral heterogeneity, and thus could not be used for clinical purposes. CONCLUSIONS: In situ BRCA1-related expression parameters could be used for clinical purposes at the time of diagnosis. In contrast, miR-548c-5p showed a promising potential as a prognostic factor in TNBC. [less ▲]Detailed reference viewed: 26 (6 ULg)
Homozygosity mapping in clinical setting : a usefull method in workup of patients born to consanguineous parents presenting with an heterogeneous autosomal recessive disorder
SEGERS, Karin ; CABERG, Jean-Hubert ; JACQUINET, Adeline et al
Poster (2013, March 15)Detailed reference viewed: 18 (1 ULg)
Rapid prenatal diagnosis of fetal Zellweger syndrome by biochemical tests, complementation studies, and molecular analyses.
SEGERS, Karin ; PIERQUIN, Geneviève ; GAILLEZ, Stephanie et al
in Prenatal Diagnosis (2013), 33(2), 201-3Detailed reference viewed: 34 (5 ULg)
Co-Occurence of two rare autosomal recessive syndromes in a young patient
SEGERS, Karin ; Debray, François-Guillaume ; et al
Poster (2011, March 04)Detailed reference viewed: 10 (4 ULg)
3-years experience review of neonatal screening for hemoglobin disorders using tandem mass spectrometry.
BOEMER, François ; Cornet, Yves ; LIBIOULLE, Cécile et al
in Clinica Chimica Acta (2011), 412(15-16), 1476-9
BACKGROUND: Neonatal screening programs for sickle cell disease are common in North America and in some European countries. Isoelectric Focusing or High Performance Liquid Chromatography is the main ... [more ▼]
BACKGROUND: Neonatal screening programs for sickle cell disease are common in North America and in some European countries. Isoelectric Focusing or High Performance Liquid Chromatography is the main technique used for hemoglobin variant detection. METHODS: Since tandem mass spectrometry is being used for screening of inherited metabolic disorders and allows protein identification, we had developed an application to identify the most relevant hemoglobin mutations with this technology. RESULTS: This approach had been previously validated and has been routinely applied in our laboratory for the last three years. We report here our experience with this new method in the field, applied to our East-Belgian population. CONCLUSIONS: To conclude, mass spectrometry provides an efficient alternative approach for laboratories performing neonatal screening of hemoglobin disorders. [less ▲]Detailed reference viewed: 62 (13 ULg)
Free sialic acid storage disease mimicking cerebral palsy and revealed by blood smear examination.
Debray, François-Guillaume ; Lefebvre, Caroline ; et al
in Journal of Pediatrics (2011), 158(1), 1651651Detailed reference viewed: 62 (5 ULg)
Molecular analysis of the FOLR genes in patients with cerebral folate deficiency
SEGERS, Karin ; ; RAMAEKERS, Vincent et al
Poster (2010, November 02)Detailed reference viewed: 4 (0 ULg)
Improved molecular diagnostics of idiopathic short stature and allied disorders: quantitative polymerase chain reaction-based copy number profiling of SHOX and pseudoautosomal region 1.
; ; et al
in Journal of Clinical Endocrinology and Metabolism (2010), 95(6), 3010-8
CONTEXT: Short stature has an incidence of three in 100 in children. Reliable molecular genetic testing may be crucial in the context of beneficial disease management. Deletions spanning or surrounding ... [more ▼]
CONTEXT: Short stature has an incidence of three in 100 in children. Reliable molecular genetic testing may be crucial in the context of beneficial disease management. Deletions spanning or surrounding the SHOX gene account for a significant proportion of patients with idiopathic short stature (ISS) and allied disorders, such as Leri-Weill dyschondrosteosis. OBJECTIVE: Several shortcomings of current strategies for copy number profiling of the SHOX region prompted us to develop an improved test for molecular diagnostics of the SHOX region. DESIGN AND RESULTS: We introduced a quantitative PCR (qPCR)-based copy number profiling test, consisting of 11 amplicons targeting clinically relevant regions, i.e. the SHOX gene and regulatory regions. To ensure an optimal sensitivity and specificity, this test was validated in 32 controls and 18 probands with previously identified copy number changes. In addition, 152 probands with SHOX-associated phenotypes were screened, revealing 10 novel copy number changes. CONCLUSION: This highly validated qPCR test supersedes other approaches for copy number screening of the SHOX region in terms of reliability, accuracy, and cost efficiency. In addition, another strong point is the fact that it can be easily implemented in any standard equipped molecular laboratory. Our qPCR-based test is highly recommended for molecular diagnostics of idiopathic short stature and allied disorders. [less ▲]Detailed reference viewed: 21 (5 ULg)
Genetic Analysis of Rwandan Patients With Cystic Fibrosis-Like Symptoms: Identification of Novel Cystic Fibrosis Transmembrane Conductance Regulator and Epithelial Sodium Channel Gene Variants.
; ; Verhaeghe, Catherine et al
in CHEST (2009), 135(5), 1233-42
Background The defect in chloride and sodium transport in cystic fibrosis (CF) patients is a consequence of CFTR loss of function and of an abnormal interaction between CFTR and ENaC. A few patients were ... [more ▼]
Background The defect in chloride and sodium transport in cystic fibrosis (CF) patients is a consequence of CFTR loss of function and of an abnormal interaction between CFTR and ENaC. A few patients were described with CF-like symptoms, a single CFTR mutation and an ENaC mutation. Methods To study African patients with CF-like symptoms and to relate the disease to gene mutations of both CFTR and ENaC genes, we collected clinical data and DNA samples from 60 African patients with a CF phenotype. The CFTR gene was first analyzed in all patients by dHPLC followed by direct sequencing, whereas the SCNN1A, SCNN1B and SCNN1G subunits of ENaC gene were analyzed by sequencing in the five patients who carried only one CF mutation. The frequency of all identified ENaC variants was established in a control group of 200 healthy individuals and in the 55 CF-like patients without any CFTR mutation Results Three CFTR mutants, including one previously undescribed missense mutation (p.A204T), and a 5T/7T variant were identified in five patients. ENaC gene sequencing in these 5 patients detected 8 ENaC variants: c.72T>C and p.V573I in SCNN1A; p.V348M, p.G442V, c.1473 + 28C>T, and p.T577T in SCNN1B; and p.S212S, c.1176 + 30G>C in SCNN1G. In the 55 CF-like patients without any CFTR mutation, we identified five of these eight ENaC variants, including the frequent p.G442V polymorphism, but we did not detect the presence of the p.V348M, p.T577T, and c.1176 + 30G>C ENaC variants. Moreover, these last three ENaC variants, p.V348M, p.T577T, and c.1176 + 30G>C, were not found in the control group. Conclusion Our data suggest that CF-like syndrome in Africa could be associated with CFTR and ENaC mutations. [less ▲]Detailed reference viewed: 263 (12 ULg)
Deletion of Xpter encompassing the SHOX gene and PAR1 region in familial patients with Leri-Weill Dyschondrosteosis syndrome.
; Vanbellinghen, Jean-François ; Hellin, Anne-Cécile et al
in Genetic Counseling (Geneva, Switzerland) (2009), 20(1), 9-17
Heterozygote deletions or mutations of pseudoautosomal 1 region (PAR1) encompassing the short stature homeobox-containing (SHOX) gene cause Leri-Weill Dyschondrosteosis (LWD), which is a dominantly ... [more ▼]
Heterozygote deletions or mutations of pseudoautosomal 1 region (PAR1) encompassing the short stature homeobox-containing (SHOX) gene cause Leri-Weill Dyschondrosteosis (LWD), which is a dominantly inherited osteochondroplasia characterized by short stature with mesomelic shortening of the upper and lower limbs and Madelung deformity of the wrists. SHOX is expressed by both sex chromosomes in males and females and plays an important role in bone growth and development. Clinically, the LWD expression is variable and more severe in females than males due to sex differences in oestrogen levels. Here, we report two familial cases of LWD with a large Xp terminal deletion (approximately 943 kb) of distal PAR1 encompassing the SHOX gene. In addition, the proband had mental retardation which appeared to be from recessive inheritance in the family. [less ▲]Detailed reference viewed: 51 (7 ULg)
Novel SACS mutation in a Belgian family with sacsin-related ataxia.
; SEGERS, Karin ; BOUQUIAUX, Olivier et al
in Journal of the Neurological Sciences (2008), 264(1-2), 73-6
The authors describe the four patients in the first known Belgian family with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). A novel homozygous missense mutation, NM_014363.3: c.3491T ... [more ▼]
The authors describe the four patients in the first known Belgian family with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). A novel homozygous missense mutation, NM_014363.3: c.3491T>A in exon 9, of the SACS gene was identified in the present family, which results in an original amino acid of methionine to lysine substitution at amino acid residue 1164 (p.M1164K). Although the cardinal clinical features, i.e., spastic ataxia with peripheral neuropathy, in our patients were similar to those in Quebec patients, our patients exhibited some atypical clinical features, e.g., teenage-onset and absence of retinal hypermyelination. The present family is from Wallonia, and there could be shared ethnicity with the families of Charlevoix-Saguenay. [less ▲]Detailed reference viewed: 45 (3 ULg)
Germline PTPN11 missense mutation in a case of Noonan syndrome associated with mediastinal and retroperitoneal neuroblastic tumors.
; Pierquin, Geneviève ; Janin, Nicolas et al
in Cancer Genetics & Cytogenetics (2008), 182(1), 40-2
Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, typical craniofacial dysmorphism, skeletal anomalies, congenital heart defects, and predisposition to malignant ... [more ▼]
Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, typical craniofacial dysmorphism, skeletal anomalies, congenital heart defects, and predisposition to malignant tumors. In approximately 50% of cases, the disease is caused by missense mutations in the PTPN11 gene. To date, solid tumors, and particularly brain tumors and rhabdomyosarcomas, have been documented in patients with NS; however, few cases of neuroblastoma associated with NS have been reported. Here we report an unusual case of neuroblastoma with mediastinal, retroperitoneal, and medullar locations associated in a NS patient carrying a PTPN11 germline missense mutation (p.G60A). This missense mutation occurs within the N-SH2 domain of the PTPN11 gene and has been reported to be associated with acute leukemia in NS patients. The association of this p.G60A PTPN11 mutation with neuroblastoma provides new evidence that gain of function PTPN11 mutations may play an important role in the pathogenesis of solid tumors associated with Noonan syndrome. [less ▲]Detailed reference viewed: 62 (11 ULg)
Spinocerebellar ataxia type 2 (SCA2): clinical features and genetic analysis.
; Pierquin, Geneviève ; Segers, Karin et al
in Journal of Tropical Pediatrics (2008), 54(5), 350-2
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease that results from the expansion of an unstable trinucleotide CAG repeat encoding for a polyglutamine tract. In ... [more ▼]
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease that results from the expansion of an unstable trinucleotide CAG repeat encoding for a polyglutamine tract. In normal individuals, alleles contain between 14 and 31 CAG repeats, whereas the pathological alleles have more than 35 CAG repeats. The clinical phenotype of SCA2 includes a progressive cerebellar ataxia with additional features such as ophthalmoplegia, extra-pyramidal or pyramidal signs and peripheral neuropathy. We report a SCA2 large African family with several affected individuals. A major pathological allele carrying 43 CAG repeats was identified in the proband. To our knowledge, this is a first report of a SCA disorder described in Central African patients, thus indicating the need to consider this diagnosis in young African ataxic patients. [less ▲]Detailed reference viewed: 58 (4 ULg)
Identification of a point mutation associated with SMA by direct sequencing of genomic DNA
SEGERS, Karin ; MATHIAS, Valérie ; GAILLEZ, Stephanie et al
Poster (2007, October 23)Detailed reference viewed: 18 (1 ULg)