Digenic Inheritance Mode in Congenital Hypothyroidism due to Thyroid Dysgenesis: HYPOTYGEN translational cohort study.

Context: Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and is chiefly caused by thyroid dysgenesis (CHTD). The inheritance mode of the disease remains complex.

Objectives: Gain insight into the inheritance mode of CHTD.

[The contribution of social networks using the example of type 1 diabetes].

Type 1 diabetes has an impact not only on physical health, but also on social life, family life and psychological balance. Social networks play a decisive role, alongside associations, in helping patients to adopt the "other pace of life" implied by the disease. Beyond health, the skills needed to enable patients to achieve personal fulfillment are beyond the scope of healthcare professionals.

Ovarian Hyperandrogenism and Response to Gonadotropin-releasing Hormone Analogues in Primary Severe Insulin Resistance.

Context: Insulin resistance (IR) is associated with polycystic ovaries and hyperandrogenism, but underpinning mechanisms are poorly understood and therapeutic options are limited.

Objective: To characterize hyperandrogenemia and ovarian pathology in primary severe IR (SIR), using IR of defined molecular etiology to interrogate disease mechanism. To extend evaluation of gonadotropin-releasing hormone (GnRH) analogue therapy in SIR.

High Diagnostic Yield of Targeted Next-Generation Sequencing in a Cohort of Patients With Congenital Hypothyroidism Due to Dyshormonogenesis.

Objective: To elucidate the molecular cause in a well-characterized cohort of patients with Congenital Hypothyroidism (CH) and Dyshormonogenesis (DH) by using targeted next-generation sequencing (TNGS).

Study Design: We studied 19 well-characterized patients diagnosed with CH and DH by targeted NGS including genes involved in thyroid hormone production. The pathogenicity of novel mutations was assessed based on prediction tool results, functional studies when possible, variant location in important protein domains, and a review of the recent literature.

Dental and craniofacial features associated with GNAS loss of function mutations.

Background: Pseudohypoparathyroidism (PHP, OMIM #103580) is a very rare disease (incidence 0.3-1/100,000). Heterozygous inactivating mutations involving the maternal GNAS exons 1-13 that encodes the alpha subunit of the stimulatory G protein (Gsα) cause inactivating parathyroid hormone (PTH)/PTHrP signalling disorder type 2 (iPPSD2 or PHP type 1A), which is characterized by Albright hereditary osteodystrophy and resistance to multiple hormones that act through the Gsα signalling pathway (including PTH, thyroid-stimulating hormone, and α-melanocyte-stimulating hormone).

Association between quality of life of adolescents with type 1 diabetes and parents' illness perception as evaluated by adolescents.

Children and adolescents account for half of all cases of type 1 diabetes, which is one of the most common pediatric chronic diseases. The disease's effects and the treatment/disease-management protocols patients must follow can lead to a marked deterioration in quality of life, especially for adolescents. Patients' illness perceptions have been shown to impact their quality of life, but do other people's illness perceptions also have an effect? The present study addressed this question by investigating possible links between the quality of life of adolescent patients with type 1 diabetes and illness perceptions, measured in terms of the adolescents' self-perceptions, parents' self-perceptions, and the adolescents' evaluations of their parents' perceptions.

Association of environmental markers with childhood type 1 diabetes mellitus revealed by a long questionnaire on early life exposures and lifestyle in a case-control study.

Background: The incidence of childhood type 1 diabetes (T1D) incidence is rising in many countries, supposedly because of changing environmental factors, which are yet largely unknown. The purpose of the study was to unravel environmental markers associated with T1D.

Methods: Cases were children with T1D from the French Isis-Diab cohort.

Neuropsychological dysfunction and developmental defects associated with genetic changes in infants with neonatal diabetes mellitus: a prospective cohort study [corrected].

Background: Neonatal diabetes mellitus is a rare genetic form of pancreatic β-cell dysfunction. We compared phenotypic features and clinical outcomes according to genetic subtypes in a cohort of patients diagnosed with neonatal diabetes mellitus before age 1 year, without β-cell autoimmunity and with normal pancreas morphology.

Methods: We prospectively investigated patients from 20 countries referred to the French Neonatal Diabetes Mellitus Study Group from 1995 to 2010.

Markers of recurrence and long-term morbidity in craniopharyngioma: a systematic analysis of 171 patients.

Context: Craniopharyngiomas are often associated with an unfavorable prognosis, but data on their long-term consequences are sparse.

Objective: The aim of the study was to identify markers of recurrence and factors associated with compromised social rehabilitation and altered quality of life in a large cohort of patients with either childhood-onset (CO) or adult-onset craniopharyngioma.

Methods: Retrospective analysis was performed for 171 patients treated for craniopharyngioma in two academic centers in France between 1972 and 2009.

GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus.

Background: The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes.

Methods: We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.

Impaired puberty, fertility, and final stature in 45,X/46,XY mixed gonadal dysgenetic patients raised as boys.

Context: Gender assignment followed by surgery and hormonal therapy is a difficult decision in the management of 45,X/46,XY patients with abnormal external genitalia at birth considering the paucity of studies evaluating pubertal development and fertility outcome, most notably for patients raised as boys.

Objective: The purpose of this study was to describe the pubertal course of 20 45,X/46,XY patients born with ambiguous genitalia and raised as boys.

Methods: This is a multicenter retrospective study.

Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: an extensive international experience of 55 patients.

Context: In 46,XY disorders of sex development, 5α-reductase deficiency is rare and is not usually the first-intention diagnosis in newborn ambiguous genitalia, contrary to partial androgen insensitivity syndrome. Yet the cause of ambiguous genitalia may guide sex assignment, and rapid, precise diagnosis of 5α-reductase deficiency is essential.

Objective: The aim of the study was to describe relevant data for clinical diagnosis, biological investigation, and molecular determination from 55 patients with srd5A2 mutations identified in our laboratory over 20 yr to improve early diagnosis.

Resistance to leptin-replacement therapy in Berardinelli-Seip congenital lipodystrophy: an immunological origin.

Context: Recently, in a 4-month proof-of-concept trial, beneficial metabolic effects were reported in non-diabetic children with Berardinelli-Seip congenital lipodystrophy (BSCL); this information prompted us to hypothesize that long-term leptin-replacement therapy might improve or reverse the early complications of the disease in these patients.

Patients And Methods: A 28-month trial was implemented in eight patients. Efficacy assessment was based on a decrease in serum triglyceride concentrations, and/or a decrease in liver volume and/or an increase in insulin sensitivity of at least 30% respectively.

Heterozygous missense mutations in the insulin gene are linked to permanent diabetes appearing in the neonatal period or in early infancy: a report from the French ND (Neonatal Diabetes) Study Group.

Objective: Permanent neonatal diabetes (PND) is defined by chronic hyperglycemia due to severe nonautoimmune insulin deficiency diagnosed in the first months of life. Several genes, including KCNJ11 and ABCC8, which encode the two subunits of the ATP-sensitive K(+) channel (K(ATP) channel) can cause PND. Mutations in the insulin (INS) gene have been recently described in families with neonatal diabetes.

Metabolic correction induced by leptin replacement treatment in young children with Berardinelli-Seip congenital lipoatrophy.

Objective: Berardinelli-Seip syndrome is a rare congenital lipoatrophy with a severe prognosis and no efficient therapy. Children present with low leptin levels and severe metabolic complications (insulin resistance, elevated triglyceride levels, and hepatic steatosis). The objective of this study was to test safety and efficacy of recombinant-methionyl-human leptin replacement in children with Berardinelli-Seip syndrome before development of severe metabolic disease

Methods: As part of an open trial, recombinant-methionyl-human leptin was given daily for 4 months to children who did not have diabetes and had Berardinelli-Seip congenital lipoatrophy and metabolic complications at a dosage that was meant to achieve physiologic levels.

Loss of constitutive activity of the growth hormone secretagogue receptor in familial short stature.

The growth hormone (GH) secretagogue receptor (GHSR) was cloned as the target of a family of synthetic molecules endowed with GH release properties. As shown recently through in vitro means, this receptor displays a constitutive activity whose clinical relevance is unknown. Although pharmacological studies have demonstrated that its endogenous ligand--ghrelin--stimulates, through the GHSR, GH secretion and appetite, the physiological importance of the GHSR-dependent pathways remains an open question that gives rise to much controversy.

Normal physical working capacity in prepubertal children with type 1 diabetes compared with healthy controls.

Background: Exercise testing has become a valuable help for the physician to examine the influence of recommended exercise training on physical fitness. However, the question as to how diabetic prepubertal children differ from their non-diabetic peers in their performance capacity has only partial and sometimes conflicting answers in the literature.

Aim And Methods: The aim of the current study was thus to evaluate aerobic fitness during an incremental submaximal test (measure of the Physical Working Capacity 170 (PWC170)) in 17 well-controlled prepubertal insulin-dependent diabetic boys aged 8.