References of "CABERG, Jean-Hubert"
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See detailSomatic mosaicism underlies X-linked acrogigantism (XLAG) syndrome in sporadic male subjects
Daly, Adrian ULg; Yuan, Bo; Fina, Frederic et al

in Endocrine-Related Cancer (2016)

Somatic mosaicism has been implicated as a causative mechanism in a number of genetic and genomic disorders. X-linked acrogigantism (XLAG) syndrome is a recently characterized genomic form of pediatric ... [more ▼]

Somatic mosaicism has been implicated as a causative mechanism in a number of genetic and genomic disorders. X-linked acrogigantism (XLAG) syndrome is a recently characterized genomic form of pediatric gigantism due to aggressive pituitary tumors that is caused by submicroscopic chromosome Xq26.3 duplications that include GPR101. We studied XLAG syndrome patients (N=18) to determine if somatic mosaicism contributed to the genomic pathophysiology. Eighteen subjects with XLAG syndrome were identified with Xq26.3 duplications using high definition array comparative genome hybridization (HD-aCGH). We noted males with XLAG had a decreased log2 ratio compared with expected values, suggesting potential mosaicism, while females showed no such decrease. As compared with familial male XLAG cases, sporadic males had more marked evidence for mosaicism, with levels of Xq26.3 duplication between 16.1-53.8%. These characteristics were replicated using a novel, personalized breakpoint-junction specific quantification droplet digital PCR (ddPCR) technique. Using a separate ddPCR technique we studied the feasibility of identifying XLAG syndrome cases in a distinct patient population of 64 unrelated subjects with acromegaly/gigantism and identified one female gigantism patient that had increased copy number variation (CNV) threshold for GPR101 that was subsequently diagnosed as having XLAG syndrome on HD-aCGH. Employing a combination of HD-aCGH and novel ddPCR approaches, we have demonstrated that XLAG syndrome can be caused by variable degrees of somatic mosaicism for duplications at chromosome Xq26.3. Somatic mosaicism was shown to occur in sporadic males but not in females with XLAG syndrome, although the clinical characteristics of the disease were similarly severe in both sexes. [less ▲]

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See detailMicrodélétions et duplications 22q11.22 distales
PIERQUIN, Geneviève ULg; CABERG, Jean-Hubert ULg; BULK, Saskia ULg

Poster (2016, February 03)

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See detailThe genetic causes of pituitary gigantism
Rostomyan, Liliya ULg; Lysy, P; Desfilles, C et al

in Abstract book - Symposium "Perspectives in Endocrinology" (2016, January)

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See detailGPR101 mutations are not a frequent cause of congenital isolated growth hormone deficiency
Castinetti, F; Daly, Adrian ULg; Stratakis, CA et al

in Hormone & Metabolic Research (2016)

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See detailGrowth hormone releasing hormone excess and blockade in X-LAG syndrome.
Daly, Adrian Francis ULg; Lysy, Philippe; Defilles, Celine et al

in Endocrine-related cancer (2016)

X-linked acrogigantism (X-LAG) syndrome is a newly-described form of inheritable pituitary gigantism that begins in early childhood and is usually associated with markedly elevated growth hormone (GH) and ... [more ▼]

X-linked acrogigantism (X-LAG) syndrome is a newly-described form of inheritable pituitary gigantism that begins in early childhood and is usually associated with markedly elevated growth hormone (GH) and prolactin secretion by mixed pituitary adenomas/hyperplasia. Microduplications on chromosome Xq26.3 including the GPR101 gene cause X-LAG syndrome. In individual cases random GH-releasing hormone (GHRH) levels have been elevated. We performed a series of hormonal profiles in a young female sporadic X-LAG syndrome patient and subsequently undertook in vitro studies of primary pituitary tumor culture following neurosurgical resection. The patient demonstrated consistently elevated circulating GHRH levels throughout preoperative testing, which was accompanied by marked GH and prolactin hypersecretion; GH demonstrated a paradoxical increase following TRH administration. In vitro, the pituitary cells showed baseline GH and prolactin release that was further stimulated by GHRH administration. Co-incubation with GHRH and the GHRH receptor antagonist, acetyl-(D-Arg(2))-GHRH (1-29) amide, blocked the GHRH-induced GH stimulation; the GHRH receptor antagonist alone significantly reduced GH release. Pasireotide, but not octreotide, inhibited GH secretion. A ghrelin receptor agonist and an inverse agonist led to modest, statistically significant increases and decreases in GH secretion, respectively. GHRH hypersecretion can accompany the pituitary abnormalities seen in X-LAG syndrome. These data suggest that the pathology of X-LAG syndrome may include hypothalamic dysregulation of GHRH secretion, which is in keeping with localization of GPR101 in the hypothalamus. Therapeutic blockade of GHRH secretion could represent a way to target the marked hormonal hypersecretion and overgrowth that characterizes X-LAG syndrome. [less ▲]

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See detailCytogenetic Studies of Rwandan Pediatric Patients Presenting with Global Developmental Delay, Intellectual Disability and/or Multiple Congenital Anomalies.
Uwineza, Annette; Hitayezu, Janvier; JAMAR, Mauricette ULg et al

in Journal of tropical pediatrics (2016)

Global developmental delay (GDD) is defined as a significant delay in two or more developmental domains: gross or fine motor, speech/language, cognitive, social/personal and activities of daily living ... [more ▼]

Global developmental delay (GDD) is defined as a significant delay in two or more developmental domains: gross or fine motor, speech/language, cognitive, social/personal and activities of daily living. Many of these children will go on to be diagnosed with intellectual disability (ID), which is most commonly defined as having an IQ <75 in addition to impairment in adaptive functioning. Cytogenetic studies have been performed in 664 Rwandan pediatric patients presenting GDD/ID and/or multiple congenital abnormalities (MCA). Karyotype analysis was performed in all patients and revealed 260 chromosomal abnormalities. The most frequent chromosomal abnormality was Down syndrome and then Edward syndrome and Patau syndrome. Other identified chromosomal abnormalities included 47,XX,+del(9)(q11), 46,XY,del(13)(q34) and 46,XX,der(22)t(10;22)(p10;p10)mat. In conclusion, our results highlight the high frequency of cytogenetically detectable abnormalities in this series, with implications for the burden on the healthcare. This study demonstrates the importance of cytogenetic analysis in patients with GDD/ID and MCA. [less ▲]

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See detailEtude moléculaire du gène AIP sur plus de 1400 individus atteints d'adénome hypophysaire
CASTERMANS, Emilie ULg; Auriemma, R; Rostomyan, Liliya ULg et al

in Abstract book - Annales d'Endocrinologie - 32ème Congrès de la Société Française d'Endocrinologie (2015, October)

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See detailThe genetic causes of pituitary gigantism
Rostomyan, Liliya ULg; Daly, Adrian ULg; PETROSSIANS, Patrick ULg et al

in Endocrine Abstracts (2015, May)

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See detailA tale of two anomalies. A paternal duplication and a maternal deletion of 15q13
BULK, Saskia ULg; Decortis, Thierry ULg; Rondia, G et al

Poster (2015, March 06)

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See detailA new case of microdeletion 14q32.3
Uwineza, Annette ULg; BULK, Saskia ULg; CABERG, Jean-Hubert ULg et al

Poster (2015, March 06)

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See detailCongenital gigantism in a girl with anterior pituitary hyperplasia : a new genes for a new disease
Lysy, PA; Daly, Adrian ULg; Brunelle, C et al

in Abstract book - 43ème Congrès Annuel de la Société Belge de Pédiatrie (2015, March)

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See detailX-Linked acro-gigantism (X-LAG) syndrome : a new form of infant-onset pituitary gigantism
Stratakis, CA; Trivellin, G; Rostomyan, Liliya ULg et al

in Abstract book - 14th International Pituitary Congress (2015, March)

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See detailDisease characteristics of patients with X-linked acrogigantism (X-LAG) syndrome
Daly, Adrian ULg; Lodish, MB; Trivellin, G et al

in Abstract book - ENDO 2015 (2015, March)

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See detailX-Linked acro-gigantism (X-LAG) due to microduplications of chromosome Xq26 : A new disorder and implications for acromegaly
Trivellin, G; Daly, AF; Faucz, FR et al

in Abstract book - ENDO 2015 (2015, March)

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See detailClinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients.
Rostomyan, Liliya ULg; Daly, Adrian ULg; PETROSSIANS, Patrick ULg et al

in Endocrine-related cancer (2015)

Despite being a classical growth disorder, pituitary gigantism has not been studied previously in a standardized way. We performed a retrospective, multicenter, international study to characterize a large ... [more ▼]

Despite being a classical growth disorder, pituitary gigantism has not been studied previously in a standardized way. We performed a retrospective, multicenter, international study to characterize a large series of pituitary gigantism patients. We included 208 patients (163 males; 78.4%) with growth hormone excess and current/previous abnormal growth velocity for age or final height >2SD above country normal means. The median onset of rapid growth was 13.0 years and occurred significantly earlier in females than in males; pituitary adenomas were diagnosed earlier in females than males (15.8 vs. 21.5 years, respectively). Adenomas were >/=10 mm (i.e. macroadenomas) in 84%, of which extrasellar extension occurred in 77% and invasion in 54%. GH/IGF-1 control was achieved in 39% during long-term follow-up. Final height was greater in those with younger age of onset, with larger tumors and higher GH levels. Later disease control was associated with a greater difference from mid-parental height (r=0.23, P=0.02). AIP mutations occurred in 29%; microduplication at Xq26.3 -X-linked acro-gigantism (X-LAG)- occurred in two familial isolated pituitary adenoma (FIPA) kindreds and in ten sporadic patients. Tumor size was not different in X-LAG, AIP mutated and genetically-negative patient groups. AIP-mutated and X-LAG patients had significantly younger age at onset and diagnosis, but disease control was worse in genetically-negative cases. Pituitary gigantism patients are characterized by male predominance and large tumors that are difficult to control. Treatment delay increases final height and symptom burden. AIP mutations and X-LAG explain many cases, but no genetic etiology is seen in >50% of cases. [less ▲]

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See detailX-linked acrogigantism (X-LAG) syndrome : Clinical Profile and Therapeutic responses
Beckers, Albert ULg; Lodish, MB; Trivellin, G et al

in Endocrine-Related Cancer (2015), 22

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See detailMutation of the iron-sulfur cluster assembly gene IBA57 causes fatal infantile leukodystrophy.
DEBRAY, François-Guillaume ULg; Stumpfig, Claudia; Vanlander, Arnaud V. et al

in Journal of inherited metabolic disease (2015)

Leukodystrophies are a heterogeneous group of severe genetic neurodegenerative disorders. A multiple mitochondrial dysfunctions syndrome was found in an infant presenting with a progressive ... [more ▼]

Leukodystrophies are a heterogeneous group of severe genetic neurodegenerative disorders. A multiple mitochondrial dysfunctions syndrome was found in an infant presenting with a progressive leukoencephalopathy. Homozygosity mapping, whole exome sequencing, and functional studies were used to define the underlying molecular defect. Respiratory chain studies in skeletal muscle isolated from the proband revealed a combined deficiency of complexes I and II. In addition, western blotting indicated lack of protein lipoylation. The combination of these findings was suggestive for a defect in the iron-sulfur (Fe/S) protein assembly pathway. SNP array identified loss of heterozygosity in large chromosomal regions, covering the NFU1 and BOLA3, and the IBA57 and ABCB10 candidate genes, in 2p15-p11.2 and 1q31.1-q42.13, respectively. A homozygous c.436C > T (p.Arg146Trp) variant was detected in IBA57 using whole exome sequencing. Complementation studies in a HeLa cell line depleted for IBA57 showed that the mutant protein with the semi-conservative amino acid exchange was unable to restore the biochemical phenotype indicating a loss-of-function mutation of IBA57. In conclusion, defects in the Fe/S protein assembly gene IBA57 can cause autosomal recessive neurodegeneration associated with progressive leukodystrophy and fatal outcome at young age. In the affected patient, the biochemical phenotype was characterized by a defect in the respiratory chain complexes I and II and a decrease in mitochondrial protein lipoylation, both resulting from impaired assembly of Fe/S clusters. [less ▲]

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See detailDiagnostic pitfall in antenatal manifestations of CPT II deficiency.
BOEMER, François ULg; DEBERG, Michelle ULg; SCHOOS, Roland ULg et al

in Clinical genetics (2015)

Carnitine palmitoyltransferase II (CPT2) deficiency is a rare inborn error of mitochondrial fatty acid metabolism associated with various phenotypes. Whereas most patients present with postnatal signs of ... [more ▼]

Carnitine palmitoyltransferase II (CPT2) deficiency is a rare inborn error of mitochondrial fatty acid metabolism associated with various phenotypes. Whereas most patients present with postnatal signs of energetic failure affecting muscle and liver, a small subset of patients presents antenatal malformations including brain dysgenesis and neuronal migration defects. Here, we report recurrence of severe cerebral dysgenesis with Dandy-Walker malformation in three successive pregnancies and review previously reported antenatal cases. Interestingly, we also report that acylcarnitines profile, tested retrospectively on the amniotic fluid of last pregnancy, was not sensitive enough to allow reliable prenatal diagnosis of CPT2 deficiency. Finally, because fetuses affected by severe cerebral malformations are frequently aborted, CPT2 deficiency may be underestimated and fatty acid oxidation disorders should be considered when faced with a fetus with Dandy-Walker anomaly or another brain dysgenesis. [less ▲]

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