References of "Vanbellinghen, Jean-François"
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See detailMutations AIP chez les jeunes patients en dessous de 30 ans avec adénome hypophysaire agressif
Beckers, Albert ULg; Tichomirowa, M.; Barlier, A. et al

in Annales d'Endocrinologie (2010, September), 71(5), 397

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See detailMutations AIP chez les jeunes patients en-dessous de 30 ans avec adénome hypophysaire agressif
Beckers, Albert ULg; Tichomirowa, M.; Barlier, A. et al

in 27ème Congrès de la Société Française d'Endocrinologie - Deauville, 29 septembre - 2 octobre 2010 (2010, September)

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See detailCyclin dependent kinase inhibitor 1B (CDKN1B) gene mutations in FIPA
Tichomirowa, M. A.; Pellegata, N. S.; Barlier, A. et al

in European Neuroendocrine Association - Liège, 22-25 septembre 2010 (2010, September)

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See detailHigh Prevalence of AIP Gene Mutations Following Focussed Screening in Young Patients with Sporadic Pituitary Macroadenomas
Tichomirowa, M. A.; Barlier, A.; Daly, Adrian ULg et al

in European Neuroendocrine Association - Liège, 22-25 septembre 2010 (2010, September)

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See detailThe role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in causing pituitary adenomas in a large cohort of children, adolescents, and patients with genetic syndromes.
Stratakis, C. A.; Tichomirowa, M. A.; Boikos, S. et al

in Clinical Genetics (2010)

The role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in causing pituitary adenomas in a large cohort of children, adolescents, and patients with genetic syndromes. The prevalence of ... [more ▼]

The role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in causing pituitary adenomas in a large cohort of children, adolescents, and patients with genetic syndromes. The prevalence of germline mutations in MEN1, AIP, PRKAR1A, CDKN1B and CDKN2CI is unknown among pediatric patients with pituitary adenomas (PA). In this study, we screened children with PA for mutations in these genes; somatic GNAS mutations were also studied in a limited number of growth hormone (GH) or prolactin (PRL)-secreting PA. We studied 74 and 6 patients with either isolated Cushing disease (CD) or GH- or PRL-secreting PA, respectively. We also screened four pediatric patients with CD, and four with GH/PRL-secreting tumors who had some syndromic features. There was one AIP mutation (p.Lys103Arg) among 74 CD patients. Two MEN1 mutations that occurred in patients with recurrent or difficult-to-treat disease were found among patients with CD. There was one MEN1 and three AIP mutations (p.Gln307ProfsX104, p.Pro114fsX, p.Lys241X) among pediatric patients with isolated GH- or PRL-secreting PA and one additional MEN1 mutation in a patient with positive family history. There were no mutations in the PRKAR1A, CDKN1B, CDKN2C or GNAS genes. Thus, germline AIP or MEN1 gene mutations are frequent among pediatric patients with GH- or PRL-secreting PA but are significantly rarer in pediatric CD; PRKAR1A mutations are not present in PA outside of Carney complex. [less ▲]

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See detailCotransplantation of mesenchymal stem cells might prevent death from graft-versus-host disease (GVHD) without abrogating graft-versus-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning.
Baron, Frédéric ULg; Lechanteur, Chantal ULg; Willems, Evelyne ULg et al

in Biology of Blood & Marrow Transplantation (2010), 16(6), 838-47

Recent studies have suggested that coinfusion of mesenchymal stem cells (MSCs) the day of hematopoietic cell transplantation (HCT) might promote engraftment and prevent graft-versus-host disease (GVHD ... [more ▼]

Recent studies have suggested that coinfusion of mesenchymal stem cells (MSCs) the day of hematopoietic cell transplantation (HCT) might promote engraftment and prevent graft-versus-host disease (GVHD) after myeloablative allogeneic HCT. This prompted us to investigate in a pilot study whether MSC infusion before HCT could allow nonmyeloablative (NMA) HCT (a transplant strategy based nearly exclusively on graft-versus-tumor effects for tumor eradication) from HLA-mismatched donors to be performed safely. Twenty patients with hematologic malignancies were given MSCs from third party unrelated donors 30-120 minutes before peripheral blood stem cells (PBSCs) from HLA-mismatched unrelated donors, after conditioning with 2 Gy total body irradiation (TBI) and fludarabine. The primary endpoint was safety, defined as a 100-day incidence of nonrelapse mortality (NRM) <35%. One patient had primary graft rejection, whereas the remaining 19 patients had sustained engraftment. The 100-day cumulative incidence of grade II-IV acute GVHD (aGVHD) was 35%, whereas 65% of the patients experienced moderate/severe chronic GVHD (cGVHD). One-year NRM (10%), relapse (30%), overall survival (OS) (80%) and progression-free survival (PFS) (60%), and 1-year incidence of death from GVHD or infection with GVHD (10%) were encouraging. These figures compare favorably with those observed in a historic group of 16 patients given HLA-mismatched PBSCs (but no MSCs) after NMA conditioning, which had a 1-year incidence of NRM of 37% (P = .02), a 1-year incidence of relapse of 25% (NS), a 1-year OS and PFS of 44% (P = .02), and 38% (P = .1), respectively, and a 1-year rate of death from GVHD or infection with GVHD of 31% (P = .04). In conclusion, our data suggest that HLA-mismatched NMA HCT with MSC coinfusion appeared to be safe. [less ▲]

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See detailClinical characteristics and therapeutic responses in patients with Germ-line AIP mutations and pituitary adenomas : An international collaborative study
Daly, Adrian ULg; Tichomirowa, Maria A.; Petrossians, Patrick ULg et al

in Journal of Clinical Endocrinology and Metabolism (2010), 95(11),

Context: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features ... [more ▼]

Context: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. <br />Objective: The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. <br />Design: This study was an international, multicenter, retrospective case collection/database analysis. <br />Setting: The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. <br />Patients: Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. <br />Results: The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy. <br />Conclusions: AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility. [less ▲]

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See detailPathophysiological mechanisms of dominant and recessive GLRA1 mutations in hyperekplexia.
Chung, Seo-Kyung; Vanbellinghen, Jean-François ULg; Mullins, Jonathan G L et al

in Journal of Neuroscience (2010), 30(28), 9612-20

Hyperekplexia is a rare, but potentially fatal, neuromotor disorder characterized by exaggerated startle reflexes and hypertonia in response to sudden, unexpected auditory or tactile stimuli. This ... [more ▼]

Hyperekplexia is a rare, but potentially fatal, neuromotor disorder characterized by exaggerated startle reflexes and hypertonia in response to sudden, unexpected auditory or tactile stimuli. This disorder is primarily caused by inherited mutations in the genes encoding the glycine receptor (GlyR) alpha1 subunit (GLRA1) and the presynaptic glycine transporter GlyT2 (SLC6A5). In this study, systematic DNA sequencing of GLRA1 in 88 new unrelated human hyperekplexia patients revealed 19 sequence variants in 30 index cases, of which 21 cases were inherited in recessive or compound heterozygote modes. This indicates that recessive hyperekplexia is far more prevalent than previous estimates. From the 19 GLRA1 sequence variants, we have investigated the functional effects of 11 novel and 2 recurrent mutations. The expression levels and functional properties of these hyperekplexia mutants were analyzed using a high-content imaging system and patch-clamp electrophysiology. When expressed in HEK293 cells, either as homomeric alpha1 or heteromeric alpha1beta GlyRs, subcellular localization defects were the major mechanism underlying recessive mutations. However, mutants without trafficking defects typically showed alterations in the glycine sensitivity suggestive of disrupted receptor function. This study also reports the first hyperekplexia mutation associated with a GlyR leak conductance, suggesting tonic channel opening as a new mechanism in neuronal ligand-gated ion channels. [less ▲]

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See detailExpression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications.
Jaffrain-Rea, M. L.; Angelini, M.; Gargano, D. et al

in Endocrine-Related Cancer (2009), 16(3), 1029-1043

Germline mutations of the aryl hydrocarbon receptor (AHR)-interacting protein (AIP) gene confer a predisposition to pituitary adenomas (PA), usually in the setting of familial isolated PA. To provide ... [more ▼]

Germline mutations of the aryl hydrocarbon receptor (AHR)-interacting protein (AIP) gene confer a predisposition to pituitary adenomas (PA), usually in the setting of familial isolated PA. To provide further insights into the possible role of AIP in pituitary tumour pathogenesis, the expression of AIP and AHR was determined by real-time RT-PCR and/or immunohistochemistry (IHC) in a large series of PA (n=103), including 17 with AIP mutations (AIP(mut)). Variable levels of AIP and AHR transcripts were detected in all PA, with a low AHR expression (P<0.0001 versus AIP). Cytoplasmic AIP and AHR were detected by IHC in 84.0 and 38.6% of PA respectively, and significantly correlated with each other (P=0.006). Nuclear AHR was detected in a minority of PA (19.7%). The highest AIP expression was observed in somatotrophinomas and non-secreting (NS) PA, and multivariate analysis in somatotrophinomas showed a significantly lower AIP immunostaining in invasive versus non-invasive cases (P=0.019). AIP expression was commonly low in other secreting PA. AIP immunostaining was abolished in a minority of AIP(mut) PA, with a frequent loss of cytoplasmic AHR and no evidence of nuclear AHR. In contrast, AIP overexpression in a subset of NS PA could be accompanied by nuclear AHR immunopositivity. We conclude that down-regulation of AIP and AHR may be involved in the aggressiveness of somatotrophinomas. Overall, IHC is a poorly sensitive tool for the screening of AIP mutations. Data obtained on AHR expression suggest that AHR signalling may be differentially affected according to PA phenotype. [less ▲]

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See detailHigh Incidence of AIP mutations in sporadic pituitary adenomas in young patients with macroadenomas
Tichomirova, M.; Daly, Adrian ULg; Jaffrain-Réa, M. L. et al

in 52 Symposium der Deutschen Gesellschaft für Endokrinologie (2009, March)

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See detailGenetic Analysis of Rwandan Patients With Cystic Fibrosis-Like Symptoms: Identification of Novel Cystic Fibrosis Transmembrane Conductance Regulator and Epithelial Sodium Channel Gene Variants.
Mutesa, Léon; Azad, Abul Kalam; Verhaeghe, Catherine ULg 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 ▲]

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See detailNon-myeloablative transplantation with CD8-depleted or unmanipulated peripheral blood stem cells: a phase II randomized trial.
Willems, Evelyne ULg; Baron, Frédéric ULg; Baudoux, Etienne ULg et al

in Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K (2009), 23(3), 608-10

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See detailDe novo interstitial duplication 4q associated with sporadic young-onset dopa-responsive parkinsonism
Garraux, Gaëtan ULg; VANBELLINGHEN, Jean-François ULg; JAMAR, Mauricette ULg et al

in Movement Disorders : Official Journal of the Movement Disorder Society (2009), 24(Suppl. 1), 138-139

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See detailAn analysis of the role of cyclin dependant kinase inhibitor 1B (CDKN1B) gene mutations in 86 families with familial isolated pituitary adenomas (FIPA)
Tichomirova, M. A.; Daly, Adrian ULg; Pujol, Julien ULg et al

in The Endocrine Society's 91st Annual Meeting : 10-13 juin 2009, Washington (2009)

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See detailTSH-secreting pituitary adenoma in a male patient with a novel missense AIP mutation
Fajardo Montanana, C.; Daly, Adrian ULg; Tichomirova, M. A. et al

in The Endocrine Society's 91st Annual Meeting : 10-13 juin 2009, Washington (2009)

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See detailHigh Incidence of AIP mutations in sporadic pituitary adenomas in young patients with macroadenomas
Tichomirova, M. A.; Daly, Adrian ULg; Barlier, A. et al

in The Endocrine Society's 91st Annual Meeting : 10-13 juin 2009, Washington (2009)

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See detailDeletion of Xpter encompassing the SHOX gene and PAR1 region in familial patients with Leri-Weill Dyschondrosteosis syndrome.
Mutesa, L.; Vanbellinghen, Jean-François ULg; Hellin, Anne-Cécile ULg 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 ▲]

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See detailCaractérisation clinique et génétique des adénomes hypophysaires familiaux isolés (FIPA).
Beckers, Albert ULg; Apetrii, P.; Daly, Adrian ULg et al

in Revue Médicale de Liège (2009), 64(S1), 15-19

Pituitary adenomas are common brain tumours at autopsy and radiological series of unselected population. Historically, few epidemiologic data regarding the prevalence of clinically apparent pituitary ... [more ▼]

Pituitary adenomas are common brain tumours at autopsy and radiological series of unselected population. Historically, few epidemiologic data regarding the prevalence of clinically apparent pituitary adenomas have been available. Recently, a cross-sectional study conducted in Liege, Belgium, noted that clinically-apparent pituitary adenomas occurred with a prevalence of 1:1064 inhabitants, which is 3.5-5 times the previously reported prevalence. Pituitary adenomas occur predominantly as sporadic tumors, but also in a familial setting or associated to some familial/isolated tumoral syndromes. The recent characterization of the novel clinical entity FIPA (Familial Isolated Pituitary Adenomas) increased the prevalence of familial pituitary adenomas which account now for about 5% of pituitary tumors. Distinct genetic mechanisms are continuously identified and increase our understanding of the complex clinical presentation and sometimes unpredictable evolution of pituitary adenomas. [less ▲]

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See detailHigh frequency of RASSF1A and RARb2 gene promoter methylation in morphologically normal endometrium adjacent to endometrioid adenocarinoma
Arafa, M.; Kridelka, Frédéric ULg; Mathias, Valérie ULg et al

in Histopathology (2008), 53(5), 525-532

Aims: To identify a DNA methylation signature of endometrioid carcinoma of the endometrium (EEC) in the early stages of endometrial carcinogenesis. <br />Methods and results: Archival biopsy specimens of ... [more ▼]

Aims: To identify a DNA methylation signature of endometrioid carcinoma of the endometrium (EEC) in the early stages of endometrial carcinogenesis. <br />Methods and results: Archival biopsy specimens of 39 EECs, 14 cases of atypical hyperplasia (AH), 11 histologically normal endometrial tissues adjacent to EECs and 24 normal control endometrial samples were retrieved. The cases were tested by quantitative methylation-specific polymerase chain reaction with primers hybridizing in the promoter regions of five genes frequently methylated in human cancer (RASSF1A, RARb2, P16, MGMT and GSTPi). Twenty-nine of 39 (74%) EECs and 7/14 (50%) AHs were methylated for the RASSF1A gene, whereas 17/39 (44%) EECs and 6/14 (43%) AHs were positive for the methylation of the RARb2 gene. No significant results were obtained for the other genes (P16, MGMT and GSTPi). Interestingly, 4/11 (36%) and 6/11 (55%) histologically normal endometrial tissues adjacent to EEC showed, respectively, RASSF1A and RARb2 gene methylation. Furthermore, these 11 specimens were microsatellite stable and showed similar proliferative, cell cycle and apoptotic mean labelling indices as the normal endometrial control tissues. <br />Conclusions: Promoter region methylation of RASSF1A and RARb2 genes is an early event in endometrial carcinogenesis. [less ▲]

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