Endocrinologie Pediatrique

UZ, Belgium

Endocrinologie Pediatrique

UZ, Belgium
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Benko S.,French Institute of Health and Medical Research | Benko S.,University of Paris Descartes | Gordon C.T.,French Institute of Health and Medical Research | Gordon C.T.,University of Paris Descartes | And 20 more authors.
Journal of Medical Genetics | Year: 2011

Background: The early gonad is bipotential and can differentiate into either a testis or an ovary. In XY embryos, the SRY gene triggers testicular differentiation and subsequent male development via its action on a single gene, SOX9. The supporting cell lineage of the bipotential gonad will differentiate as testicular Sertoli cells if SOX9 is expressed and conversely will differentiate as ovarian granulosa cells when SOX9 expression is switched off. Results: Through copy number variation mapping this study identified duplications upstream of the SOX9 gene in three families with an isolated 46, XX disorder of sex development (DSD) and an overlapping deletion in one family with two probands with an isolated 46, XY DSD. The region of overlap between these genomic alterations, and previously reported deletions and duplications at the SOX9 locus associated with syndromic and isolated cases of 46, XX and 46, XY DSD, reveal a minimal noncoding 78 kb sex determining region located in a gene desert 517-595 kb upstream of the SOX9 promoter. Conclusions: These data indicate that a non-coding regulatory region critical for gonadal SOX9 expression and subsequent normal sex development is located far upstream of the SOX9 promoter. Its copy number variations are the genetic basis of isolated 46, XX and 46, XY DSDs of variable severity (ranging from mild to complete sex reversal). It is proposed that this region contains a gonad specific SOX9 transcriptional enhancer(s), the gain or loss of which results in genomic imbalance sufficient to activate or inactivate SOX9 gonadal expression in a tissue specific manner, switch sex determination, and result in isolated DSD.


Vitamin D deficiency occurs rather commonly among healthy pregnant women, newborns and young children, especially in certain risk groups. Since vitamin D plays a role in calcium and phosphor metabolism essential for bone health and in the physiopathology of some autoimmune diseases it seems important to provide recommendations for prevention of vitamin D deficiency. Risk factors include maternal vitamin D deficiency, low intake of fortified food, eg. breastfeeding, low compliance of supplementation, dark skin, inadequate sun exposure, premature birth, overweight, living at high latitude. The aim of this paper is to summarize available data of vitamin D sources, known situations in which deficiency is common and published guidelines on vitamin D supplementation, and translate this information in recommendations for prevention of vitamin D deficiency in healthy paediatric population in Flanders. Infants should receive an oral supplementation of 400 IU/day of vitamin D from birth and this should be continued till the age of 6 years. In cases of dark skin the dose should be 600 IU/day. An healthy life style with outdoor activities and associated sun exposure and intake of fortified nutrition should be advised. The implementation should be promoted by all healthcare professionals working with young children.


Tachon G.,CHRU Arnaud de Villeneuve | Tachon G.,Laboratoire Of Genetique Chromosomique | Lefort G.,Laboratoire Of Genetique Chromosomique | Puechberty J.,CHRU Arnaud de Villeneuve | And 10 more authors.
Human Reproduction | Year: 2014

We report a case of discordant phenotypic sex in monozygotic twins mosaic 47,XXY/46,XX: monozygotic heterokaryotypic twins. The twins presented with cognitive and comprehension delay, behavioural and language disorders, all symptoms frequently reported in Klinefelter syndrome. Molecular zygosity analysis with several markers confirmed that the twins are in effect monozygotic (MZ). Array comparative genomic hybridization found no evidence for the implication of copy number variation in the phenotypes. Ultrasound scans of the reproductive organs revealed no abnormalities. Endocrine tests showed a low testosterone level in Twin 1 (male phenotype) and a low gonadotrophin level in Twin 2 (female phenotype) which, combined with the results from ultrasound examination, provided useful information for potentially predicting the future fertility potential of the twins. Blood karyotypes revealed the presence of a normal 46,XX cell line and an aneuploïd 47,XXY cell line in both patients. Examination of the chromosome constitutions of various tissues such as blood, buccal smear and urinary sediment not surprisingly showed different proportions for the 46,XX and 47,XXY cell lines, which most likely explains the discordant phenotypic sex and mild Klinefelter features. The most plausible underlying biological mechanism is a post-zygotic loss of the Y chromosome in an initially 47,XXY zygote. This would result in an embryo with both 46,XX and 47,XXY cells lines which could subsequently divide into two monozygotic embryos through a twinning process. The two cell lines would then be distributed differently between tissues which could result in phenotypic discordances in the twins. These observations emphasize the importance of regular paediatric evaluations to determine the optimal timing for fertility preservation measures and to detect new Klinefelter features which could appear throughout childhood in the two subjects. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.


PubMed | Montpellier University, Unite Medicale des Maladies Auto inflammatoire, Laboratoire Of Genetique Chromosomique, Service de Radiopediatrie and 2 more.
Type: Case Reports | Journal: Human reproduction (Oxford, England) | Year: 2014

We report a case of discordant phenotypic sex in monozygotic twins mosaic 47,XXY/46,XX: monozygotic heterokaryotypic twins. The twins presented with cognitive and comprehension delay, behavioural and language disorders, all symptoms frequently reported in Klinefelter syndrome. Molecular zygosity analysis with several markers confirmed that the twins are in effect monozygotic (MZ). Array comparative genomic hybridization found no evidence for the implication of copy number variation in the phenotypes. Ultrasound scans of the reproductive organs revealed no abnormalities. Endocrine tests showed a low testosterone level in Twin 1 (male phenotype) and a low gonadotrophin level in Twin 2 (female phenotype) which, combined with the results from ultrasound examination, provided useful information for potentially predicting the future fertility potential of the twins. Blood karyotypes revealed the presence of a normal 46,XX cell line and an aneuplod 47,XXY cell line in both patients. Examination of the chromosome constitutions of various tissues such as blood, buccal smear and urinary sediment not surprisingly showed different proportions for the 46,XX and 47,XXY cell lines, which most likely explains the discordant phenotypic sex and mild Klinefelter features. The most plausible underlying biological mechanism is a post-zygotic loss of the Y chromosome in an initially 47,XXY zygote. This would result in an embryo with both 46,XX and 47,XXY cells lines which could subsequently divide into two monozygotic embryos through a twinning process. The two cell lines would then be distributed differently between tissues which could result in phenotypic discordances in the twins. These observations emphasize the importance of regular paediatric evaluations to determine the optimal timing for fertility preservation measures and to detect new Klinefelter features which could appear throughout childhood in the two subjects.


Pineau J.-C.,French National Center for Scientific Research | Lalys L.,French National Center for Scientific Research | Bocquet M.,CNRS Process and Engineering in Mechanics and Materials Laboratory | Guihard-Costa A.-M.,French National Center for Scientific Research | And 4 more authors.
Annals of Nutrition and Metabolism | Year: 2010

Background/Aims: To compare body fat (BF) measurements obtained with a new ultrasound method with those assessed by dual-energy X-ray absorptiometry (DEXA) in obese adolescents. Methods: In 94 adolescents (57 females and 37 males) aged 12-19 years and body mass index (BMI) exceeding 30 kg·m-2, the z-score BMI for age was 6.7 (adolescent girls) and 6.6 (adolescent boys) >97th percentile. BF was measured using DEXA and a method based on ultrasound measurements, body weight, height, abdominal circumference and mid-thigh circumference. Results: Obesity class I was noted in 39%, II in 28% and III in 33% of the patients. BF by ultrasound correlated closely with BF by DEXA, in both females (r = 0.958) and males (r = 0.981), with standard errors of the estimates (SEE) being 2.9 and 2.5 kg, respectively. The ultrasound method was more accurate than the skinfold technique (n = 24; SEE: 2.2 vs. 6.5 kg, respectively). In 13 adolescents who had marked weight loss after 6 months of treatment, the decrease in DEXA-measured BF correlated closely with the decrease in ultrasound-measured BF (r = 0.95). Conclusions: Our innovative portable ultrasound technique has advantages in terms of reliability, reproducibility, accuracy and costs for screening and monitoring obese adolescents. A patent application has been submitted. Our method should prove valuable for epidemiological studies. © 2010 S. Karger AG, Basel.


Philibert P.,Montpellier University | Biason-Lauber A.,Endocrinologie Pediatrique | Gueorguieva I.,Toulouse University Hospital Center | Stuckens C.,Toulouse University Hospital Center | And 6 more authors.
Fertility and Sterility | Year: 2011

In a collaborative study, we investigated four 46, XX adolescent girls with Mayer-Rokitansky-Küster-Hauser syndrome and hyperandrogenism. Molecular analysis of the WNT4 gene permitted us to identify a new mutation (p.A233T). Functional studies revealed partial repression of steroidogenic enzymes (normal repression of HSD3B2) contrasting with the abnormal reexpression of CYP17A1 enzyme in the OVCAR3 cell line. This fourth new WNT4 mutation confirms that this signaling molecule is involved in mullerian development and androgen biosynthesis repression in the ovary. Interestingly, this mutant partially lacks the capability to repress ovarian steroidogenic enzymes, with abnormal expression of 17α-hydroxylase. © 2011 by American Society for Reproductive Medicine.


Tran Mau-Them F.,Montpellier University | Boualam A.,Montpellier University | Barat-Houari M.,Laboratoire des maladies rares et auto inflammatoire | Jeandel C.,Endocrinologie pediatrique | And 14 more authors.
American Journal of Medical Genetics, Part A | Year: 2014

Dysspondyloenchondromatosis is a rare form of generalized enchondromatosis associated with spinal involvement. This skeletal dysplasia is characterized by multiple enchondromas present in vertebrae as well as in metaphyseal and diaphyseal parts of the long tubular bones, post-natal short stature, and early development of kyphoscoliosis. A novel heterozygous missense mutation in COL2A1 was recently identified in a patient with dysspondyloenchondromatosis. This suggests that dysspondyloenchondromatosis might expand the already broad spectrum of type II collagenopathies. Here, we report on a young girl with features of dysspondyloenchondromatosis, specifically short stature, thoracoscoliosis, and generalized enchondromas lesions. Sanger sequencing failed to detect a mutation in COL2A1. We therefore suggest that dysspondyloenchondromatosis is a genetically heterogeneous condition. © 2013 Wiley Periodicals, Inc.

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