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.

Differential alternative splicing analysis links variation in ZRSR2 to a novel type of oral-facial-digital syndrome.

Purpose: Oral-facial-digital (OFD) syndromes are genetically heterogeneous developmental disorders, caused by pathogenic variants in genes involved in primary cilia formation and function. We identified a previously undescribed type of OFD with brain anomalies, ranging from alobar holoprosencephaly to pituitary anomalies, in 6 unrelated families.

Methods: Exome sequencing of affected probands was supplemented with alternative splicing analysis in patient and control lymphoblastoid and fibroblast cell lines, and primary cilia structure analysis in patient fibroblasts.

Steroidogenic cell microenvironment and adrenal function in physiological and pathophysiological conditions.

The human adrenal cortex is a complex organ which is composed of various cell types including not only steroidogenic cells but also mesenchymal cells, immunocompetent cells and neurons. Intermingling of these diverse cell populations favors cell-to-cell communication processes involving local release of numerous bioactive signals such as biogenic amines, cytokines and neuropeptides. The resulting paracrine interactions play an important role in the regulation of adrenocortical cell functions both in physiological and pathophysiological conditions.

Early Effect of Supplemented Infant Formulae on Intestinal Biomarkers and Microbiota: A Randomized Clinical Trial.

Background: Post-natal gut maturation in infants interrelates maturation of the morphology, digestive, and immunological functions and gut microbiota development. Here, we explored both microbiota development and markers of gut barrier and maturation in healthy term infants during their early life to assess the interconnection of gut functions during different infant formulae regimes.

Methods: A total of 203 infants were enrolled in this randomized double-blind controlled trial including a breastfed reference group.

Role of Mast Cells in the Control of Aldosterone Secretion.

Mast cells are immune cells present in adrenals from various species. Proliferation and activation of adrenal mast cells seem to be influenced by environment, since they increase during summer and in response to sodium restriction in frogs and mouse, respectively. Although the physiological factors regulating adrenal mast cell activity have not been identified, they might involve neurotransmitters and the renin-angiotensin system.

Paracrine Regulation of Aldosterone Secretion in Physiological and Pathophysiological Conditions.

Aldosterone secretion by the zona glomerulosa of the adrenal cortex is controlled by circulating factors including the renin angiotensin system (RAS) and potassium. Mineralocorticoid production is also regulated through an autocrine/paracrine mechanism by a wide variety of bioactive signals released in the vicinity of adrenocortical cells by chromaffin cells, nerve endings, cells of the immune system, endothelial cells and adipocytes. These regulatory factors include conventional neurotransmitters and neuropeptides.

Molecular characterization of a recurrent 10.9 kb CYP24A1 deletion in Idiopathic Infantile Hypercalcemia.

Loss-of-function mutations in CYP24A1 (MIM 126065 20q13.2), the gene encoding the 24-hydroxylase responsible for 25-OH-D and 1,25-(OH)D degradation, are identified in about 20% of patients presenting Idiopathic Infantile Hypercalcemia (IIH) (MIM 143880). Common features of this autosomal recessive condition included hypercalcemia with hypercalciuria, suppressed PTH and a high 25-OH-D:24,25-(OH)D ratio.

Fertility Preservation in Klinefelter Syndrome Patients during the Transition Period.

Spermatozoa have occasionally been identified in ejaculate of adult Klinefelter syndrome (KS) patients but very exceptionally in KS adolescents. Spermatozoa can also be retrieved in testicular tissue of KS adolescents. The testis may also harbor spermatogonia and noncompletely differentiated germ cells.

mutations are responsible for autosomal recessive osteogenesis imperfecta.

Background: Stüve-Wiedemann syndrome (SWS) is characterised by bowing of the lower limbs, respiratory distress and hyperthermia that are often responsible for early death. Survivors develop progressive scoliosis and spontaneous fractures. We previously identified mutations in most SWS cases, but absence of pathogenic changes in five patients led us to perform exome sequencing and to identify homozygosity for a mutation in one case [p.

Temporal and spatial distribution of mast cells and steroidogenic enzymes in the human fetal adrenal.

Mast cells are present in the human adult adrenal with a potential role in the regulation of aldosterone secretion in both normal cortex and adrenocortical adenomas. We have investigated the human developing adrenal gland for the presence of mast cells in parallel with steroidogenic enzymes profile and serotonin signaling pathway. RT-QPCR and immunohistochemical studies were performed on adrenals at 16-41 weeks of gestation (WG).

Metallic Profile of Whole Blood and Plasma in a Series of 99 Healthy Children.

In recent years, special emphasis has been put on heavy metals. Children are very sensitive to accumulation of metals. Furthermore, as regards elements, the reference values in children are scarce in the literature as it is difficult to obtain the large quantity of blood necessary to analyze many metals by the conventional atomic absorption spectrometry technique.

Pharmacokinetic study of metopimazine by oral route in children.

Metopimazine (MPZ) is an antiemetic considered as a currently used drug. In France, it has become the leading antiemetic mediator due to its good tolerance, however, its pharmacokinetics has never previously been studied in children. MPZ was administered by oral route to 8 children with a single dose of 0.

Natural history and management of congenital hypothyroidism with in situ thyroid gland.

Background/objective: Normally sited glands account for increasing congenital hypothyroidism (CH). Mechanisms often remain unknown. To report the incidence of CH with in situ thyroid gland (ISTG) and describe the natural history of the disease without known etiology.

Molecular insights into the possible role of Kir4.1 and Kir5.1 in thyroid hormone biosynthesis.

Introduction: Thyroid morphogenesis is a complex process. Inwardly rectifying potassium (Kir) genes play a role in hormone release, cell excitability, pH and K(+) homeostasis in many tissues.

Objectives: To investigate the thyroid developmental expression of three members, Kir4.

Extreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutations.

Context: Within the last two decades, heterozygous loss-of-function PAX8 mutations have been reported in patients with a wide degree of thyroid gland dysfunction and growth despite the presence of identical mutations.

Objectives: To search for PAX8 mutations in a cohort of patients with congenital hypothyroidism (CH) and various types of thyroid gland defects.

Design: A cross-sectional study was conducted in a cohort of patients.

Functional characterization of the novel sequence variant p.S304R in the hinge region of TSHR in a congenital hypothyroidism patients and analogy with other formerly known mutations of this gene portion.

Context: Thyroid dysgenesis may be associated with loss-of-function mutations in the thyrotropin receptor (TSHR) gene.

Objectives: The aim of this study was to characterize a novel TSHR gene variant found in one patient harboring congenital hypothyroidism (CH) from a cohort of patients with various types of thyroid defects.

Materials And Methods: This cross-sectional cohort study involved 118 patients with CH and their family members, including 45 with familial and 73 with sporadic diseases.

[Adolescents consulting at the pediatric emergency room for psychological or psychiatric reasons].

Introduction: The number of pediatric emergency consultations for psychological or psychiatric reasons continues to rise, raising the question of the adequacy of existing facilities. Our aim was therefore to identify and characterize a population of adolescents consulting at the pediatric emergency unit at Rouen university hospital.

Methods: This study was conducted from 1 January to 31 December 2006.

A novel FOXE1 mutation (R73S) in Bamforth-Lazarus syndrome causing increased thyroidal gene expression.

Background: Homozygous loss-of-function mutations in the FOXE1 gene have been reported in several patients with partial or complete Bamforth-Lazarus syndrome: congenital hypothyroidism (CH) with thyroid dysgenesis (usually athyreosis), cleft palate, spiky hair, with or without choanal atresia, and bifid epiglottis. Here, our objective was to evaluate potential functional consequences of a FOXE1 mutation in a patient with a similar clinical phenotype.

Methods: FOXE1 was sequenced in eight patients with thyroid dysgenesis and cleft palate.

Lightwood syndrome revisited with a novel mutation in CYP24 and vitamin D supplement recommendations.

A novel mutation in CYP24A1 provides insight into idiopathic infantile hypercalcemia. In this report of 3 brothers, in twins supplemented with vitamin D (1900 IU/d), only the twin homozygous for CYP24A1 exhibited idiopathic infantile hypercalcemia. A subsequently affected younger brother given vitamin D 400 IU/d was not hypercalcemic.

The feasibility of fertility preservation in adolescents with Klinefelter syndrome.

Study Question: Is fertility preservation feasible after the onset of puberty in adolescents with Klinefelter syndrome (KS)?

Summary Answer: Fertility preservation counseling should be an integral part of the care of XXY adolescents. Frozen ejaculated or testicular spermatozoa and even frozen immature germ cells can give them the potential to conceive their genetic progeny. However, no biological or clinical parameters were predictive of mature or immature germ cell retrieval.

[Prophylactic prescription of vitamin D in France: national multicenter epidemiological study of 3240 children under 6 years of age].

Aims: The aim of the study was to assess compliance with the current recommendations of prophylactic prescription of vitamin D via a multicentric cross-sectional epidemiological survey of 3240 children under 6 years of age.

Method: Parent questionnaires and data from the health records of children presenting to the emergency departments of 25 teaching hospitals and hospital centers provided information on the children's characteristics, their prescriptions, and other vitamin D intake. Based on the currently applicable recommendations, intakes of 600-1,200 IU/day - 900-1500 IU/day for children with pigmented skin and/or premature and/or hypotrophic children - are considered adequate.