Gender differences and inflammation: an in vitro model of blood cells stimulation in prepubescent children

Gender influences clinical presentations and markers in inflammatory diseases. In many chronic conditions, frequency of complications is greater in females, suggesting that continuous inflammatory reaction may induce greater damage in targeted organs and functions.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Six Novel Variants in the MKRN3 Gene Causing Central Precocious Puberty.

peer reviewed[en] CONTEXT: Idiopathic central precocious puberty (iCPP) is defined by the premature reactivation of the hypothalamic-pituitary-gonadal axis with normal magnetic resonance imaging scan of the central nervous system, causing the development of secondary sexual characteristics before age 8 years in girls and 9 years in boys. MKRN3 loss of function variants now represent the most common genetic cause of iCPP. OBJECTIVE: This work aims to document the clinical course of puberty in 8 families harboring pathogenic MKRN3 variants. METHODS: This is an observational case series study of patients with CPP due to MKRN3 variants followed in a single center. RESULTS: Genetic analysis of MKRN3 was carried out in 28 unrelated patients with iCPP and a family history of paternal inheritance or no/unavailable maternal inheritance, particularly in case of very early and rapidly evolving CPP. We identified 6 novel and 2 recently described variants in the MKRN3 gene in 9 girls, 1 boy, and their family members. These mutations were all predicted to be deleterious by in silico prediction programs. CONCLUSION: We have identified 6 novel MKRN3 mutations in children with CPP. An MKRN3 loss of function should be considered after careful history pinpointing paternally inherited CPP. A family segregation study allowed the detection of an MKRN3 variant in 2 young brothers still prepubertal, raising the question of screening and management of asymptomatic prepubertal family members

Insight into the role of TXNRD2 in steroidogenesis through a novel homozygous TXNRD2 splice variant.

OBJECTIVE Adrenal cortisol production occurs through a biosynthetic pathway which depend on NADH and NADPH for energy supply. The mitochondrial respiratory chain and the reactive oxygen species (ROS) detoxification system are therefore important for steroidogenesis. Mitochondrial dysfunction leading to oxidative stress has been implicated in the pathogenesis of several adrenal conditions. Nonetheless, only very few patients with variants in one gene of the ROS detoxification system, Thioredoxin Reductase 2 (TXNRD2), have been described with variable phenotypes. DESIGN Clinical, genetic, structural and functional characterization of a novel, bi-allelic TXNRD2 splice variant. METHODS On human biomaterial, we performed whole exome sequencing to identify and RNA analysis to characterize the specific TXNRD2 splice variant. Amino acid conservation analysis and protein structure modeling were performed in silico. Using patient's fibroblast-derived human induced pluripotent stem cells, we generated adrenal-like cells (iALC) to study the impact of wild-type (WT) and mutant TXNRD2 on adrenal steroidogenesis and ROS production. RESULTS The patient had a complex phenotype of primary adrenal insufficiency (PAI), combined with genital, ophthalmological and neurological features. He carried a homozygous splice variant c.1348-1G>T in TXNRD2 which leads to a shorter protein lacking the C-terminus and thereby affecting homodimerization and FAD binding. Patient-derived iALC showed loss of cortisol production with overall diminished adrenal steroidogenesis, while ROS production was significantly increased. CONCLUSION Lack of TXNRD2 activity for mitochondrial ROS detoxification affects adrenal steroidogenesis and predominantly cortisol production

Growth response of syndromic versus non-syndromic children born small for gestational age (SGA) to growth hormone therapy: a Belgian study

IntroductionA substantial proportion of SGA patients present with a syndrome underlying their growth restriction. Most SGA cohorts comprise both syndromic and non-syndromic patients impeding delineation of the recombinant human growth hormone (rhGH) response. We present a detailed characterization of a SGA cohort and analyze rhGH response based on adult height (AH).MethodsClinical and auxological data of SGA patients treated with rhGH, who had reached AH, were retrieved from BELGROW, a national database of all rhGH treated patients held by BESPEED (BElgian Society for PEdiatric Endocrinology and Diabetology). SGA patients were categorized in syndromic or non-syndromic patients.Results272 patients were included, 42 classified as syndromic (most frequent diagnosis (n=6): fetal alcohol syndrome and Silver-Russell syndrome). Compared with non-syndromic patients, syndromic were younger [years (median (P10/P90)] 7.43 (4.3/12.37) vs 10.21 (5.43/14.03), p=0.0005), shorter (height SDS -3.39 (-5.6/-2.62) vs -3.07 (-3.74/-2.62), p=0.0253) and thinner (BMI -1.70 (-3.67/0.04) vs -1.14 (-2.47/0.27) SDS, p=0.0054) at start of rhGH treatment. First year rhGH response was comparable (delta height SDS +0.54 (0.24/0.94) vs +0.56 (0.26/0.92), p=0.94). Growth pattern differed with syndromic patients having a higher prepubertal (SDS +1.26 vs +0.83, p=0.0048), but a lower pubertal height gain compared to the non-syndromic group (SDS -0.28 vs 0.44, p=0.0001). Mean rhGH dose was higher in syndromic SGA patients (mg/kg body weight/day 0.047 (0.039/0.064) vs 0.043 (0.035/0.056), p=0.0042). AH SDS was lower in syndromic SGA patients (-2.59 (-4.99/-1.57) vs -2.32 (-3.3/-1.2), p=0.0107). The majority in both groups remained short (<-2 SDS: syndromic 71%, non-syndromic 63%). Total height gain was comparable in both groups (delta height SDS +0.76 (-0.70/1.48) vs +0.86 (-0.12/1.86), p=0.41).ConclusionsCompared to non-syndromic SGA patients, syndromic SGA patients were shorter when starting rhGH therapy, started rhGH therapy earlier, and received a higher dose of rhGH. At AH, syndromic SGA patients were shorter than non-syndromic ones, but their height gain under rhGH therapy was comparable

The control of linear bone growth: auxological studies in patients with growth disorders and molecular studies in an experimental rabbit model

Doctorat en sciences médicalesinfo:eu-repo/semantics/nonPublishe

Les hypoglycémies de l'enfant

In infants and children, the delicate equilibrium between glucose production and glucose utilization can easily be disrupted. This leads to hypoglycemia with the risk of brain damage. The symptoms of hypoglycemia are non specific, particularly in the infant and the young child. The definition, the pathophysiology and the different etiologies of hypoglycemia are discussed. An approach of the causes of the hypoglycemia is proposed, which depends crucially on concomitant determinations of some hormones such as insulin, cortisol and growth hormone, and metabolic factors such as ketotic bodies, at the time of hypoglycemia. Therapeutic aspects will also be briefly reviewed.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Le contrôle de la croissance linéaire osseuse :Études auxologiques chez des patients avec anomalie de la croissance et études moléculaires dans un modèle animal experimental

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The control of linear bone growth: auxological studies in patients with growth disorders and molecular studies in an experimental rabbit model

Doctorat en sciences médicalesinfo:eu-repo/semantics/nonPublishe

Les enfants nes dysmatures. Quelle evolution staturale a long terme? Quelles possibilites therapeutiques?

Intrauterine growth retardation (IUGR), defined as birth weight and/or length less than 3th percentile (P) or less than - 2 standard deviations (SD), concerns about 3 % of newborns. About 85 % born IUGR show spontaneous postnatal catch-up to a height > P3 or > - 2 SD during the first two years of life. After the age of 4 year, the children without catch-up will remain short up to final height. Classical growth hormone (GH) deficiency usually does not seem responsible for the absence of catch-up in those children. A two-year GH therapy at supraphysiological doses increases growth velocity. The effect of this treatment on final height remains to be studied, as well as optimal treatment's modalities. Attention should be paid on the possible side-effects. Finally, the evaluation of the psychological impact of GH treatment will be critical.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Familial congenital hypothyroidism: report of two patients with TSH unresponsiveness caused by a mutation in the TSH receptor gene

info:eu-repo/semantics/publishe