Imagine Institute Affiliate

France

Imagine Institute Affiliate

France

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Flechtner I.,Imagine Institute Affiliate | Lambot-Juhan K.,University of Paris Descartes | Teissier R.,Brest University Hospital Center | Colmenares A.,Imagine Institute Affiliate | And 11 more authors.
European Journal of Endocrinology | Year: 2014

Objective: To assess the prevalence of skeletal dysplasias (SDs) in patients with idiopathic short stature (ISS) or small for gestational age (SGA) status. Setting: Rare Endocrine/Growth Diseases Center in Paris, France. Design: A prospective study on consecutive patients with ISS and SGA enrolled from 2004 to 2009. Method:We used a standardized workup to classify patients into well-established diagnostic categories. Of 713 patients with ISS (nZ417) or SGA status (nZ296), 50.9% underwent a skeletal survey. We chose patients labeled normal or with a prepubertal slowdown of growth as a comparison group. Results: Diagnoses were ISS (16.9%), SGA (13.5%), normal growth (24.5%), transient growth rate slowing (17.3%), endocrine dysfunction (12%), genetic syndrome (8.9%), chronic disease (5.1%), and known SD (1.8%). SD was found in 20.9% of SGA and 21.8% ISS patients and in only 13.2% in our comparison group. SD prevalence was significantly higher in the ISS group than in the comparison group, especially (50%) for patients having at least one parent whose height was >-2 SDS. Dyschondrosteosis and hypochondroplasia were the most frequently identified SD, and genetic anomaly was found in 61.5 and 30% respectively. Subtle SD was found equally in the three groups and require long-term growth follow-up to evaluate the impact on final height. Conclusion: SD may explain more than 20% of cases of growth retardation ascribed to ISS or SGA, and this proportion is higher when parental height is!K2 SDS. A skeletal survey should be obtained in patients with delayed growth in a context of ISS or SGA. © 2014 European Society of Endocrinology Printed in Great Britain.


PubMed | IMAGINE Institute affiliate, University of Paris Pantheon Sorbonne, Endocrine and Metabolic Surgery, University of Toledo and 2 more.
Type: | Journal: Human molecular genetics | Year: 2016

Congenital hypothyroidism is the most common neonatal endocrine disorder and is primarily caused by developmental abnormalities otherwise known as thyroid dysgenesis (TD). We performed whole exome sequencing (WES) in a consanguineous family with TD and subsequently sequenced a cohort of 134 probands with TD to identify genetic factors predisposing to the disease. We identified the novel missense mutations p.S148F, p.R114Q and p.L177W in the BOREALIN gene in TD-affected families. Borealin is a major component of the Chromosomal Passenger Complex (CPC) with well-known functions in mitosis. Further analysis of the missense mutations showed no apparent effects on mitosis. In contrast, expression of the mutants in human thyrocytes resulted in defects in adhesion and migration with corresponding changes in gene expression suggesting others functions for this mitotic protein. These results were well correlated with the same genes expression pattern analyzed in the thyroid tissue of the patient with BOREALIN-p.R114W. These studies open new avenues in the genetics of TD in humans.


PubMed | Imagine Institute Affiliate
Type: Journal Article | Journal: European journal of endocrinology | Year: 2014

To assess the prevalence of skeletal dysplasias (SDs) in patients with idiopathic short stature (ISS) or small for gestational age (SGA) status.Rare Endocrine/Growth Diseases Center in Paris, France.A prospective study on consecutive patients with ISS and SGA enrolled from 2004 to 2009.We used a standardized workup to classify patients into well-established diagnostic categories. Of 713 patients with ISS (n=417) or SGA status (n=296), 50.9% underwent a skeletal survey. We chose patients labeled normal or with a prepubertal slowdown of growth as a comparison group.Diagnoses were ISS (16.9%), SGA (13.5%), normal growth (24.5%), transient growth rate slowing (17.3%), endocrine dysfunction (12%), genetic syndrome (8.9%), chronic disease (5.1%), and known SD (1.8%). SD was found in 20.9% of SGA and 21.8% ISS patients and in only 13.2% in our comparison group. SD prevalence was significantly higher in the ISS group than in the comparison group, especially (50%) for patients having at least one parent whose height was <-2 SDS. Dyschondrosteosis and hypochondroplasia were the most frequently identified SD, and genetic anomaly was found in 61.5 and 30% respectively. Subtle SD was found equally in the three groups and require long-term growth follow-up to evaluate the impact on final height.SD may explain more than 20% of cases of growth retardation ascribed to ISS or SGA, and this proportion is higher when parental height is <-2 SDS. A skeletal survey should be obtained in patients with delayed growth in a context of ISS or SGA.

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