Differential Methylation of CYP11B1 in Girls with High DHEAS Levels and correlation with 11-Oxyandrogen levels: a pilot study.

Introduction: Premature adrenarche in girls is defined biochemically by an increase in adrenal androgen (DHEAS) levels above the age-specific reference range before age 8 years. Recently, increased levels of 11-oxyandrogens have also been reported in girls with premature adrenarche. Epigenetic modifications, specifically CpG methylation, may affect gene expression and/or activity of steroidogenic enzymes during developmental changes in adrenal androgen secretion.

Joint models reveal genetic architecture of pubertal stage transitions and their association with BMI in admixed Chilean population.

Early or late pubertal onset can lead to disease in adulthood, including cancer, obesity, type 2 diabetes, metabolic disorders, bone fractures, and psychopathologies. Thus, knowing the age at which puberty is attained is crucial as it can serve as a risk factor for future diseases. Pubertal development is divided into five stages of sexual maturation in boys and girls according to the standardized Tanner scale.

Post menarcheal growth patterns in a contemporary cohort of Latino girls.

Introduction: Menarche is the last stage of pubertal development, which coincides with the completion of longitudinal growth. As a consequence of the lack of national and up-to-date data related to post-menarcheal (PM) growth, the aim of our work was to evaluate post menarcheal growth in a group of contemporary healthy Chilean girls followed, prospectively, until 4 years post-menarche.

Methods: This study was nested within the GOCS cohort, in a prospective fashion.

Association between plasma leptin/adiponectin ratio and insulin resistance indexes in prepubertal children.

Objective: To assess the association between leptin/adiponectin ratio (LAR) and insulin resistance surrogates in prepubertal children.

Materials And Methods: Study based on data from the Growth and Obesity Chilean Cohort Study (GOCS) involving 968 Chilean prepubertal children. Plasma insulin, leptin, and adiponectin were determined by immunoassays.

Identifying patient-related predictors of permanent growth hormone deficiency.

Objective: Isolated childhood growth hormone deficiency (GHD) can persist into adulthood, and re-testing at the transition period is needed to determine whether continued growth hormone therapy is indicated. Here, our objective was to identify predictors of permanent GHD.

Design: Retrospective single-centre study of patients with childhood-onset GHD who were re-tested after adult height attainment.

Association Between Markers of Adiposity During Childhood and Puberty Onset in Latino Girls.

Context: Prepubertal adiposity is associated with earlier puberty. It is unclear when this association starts, if all adiposity markers are similarly associated, and whether all pubertal milestones are similarly affected.

Objective: To evaluate the association between different adiposity markers during childhood and the timing of different pubertal milestones in Latino girls.

Differential methylation pattern in pubertal girls associated with biochemical premature adrenarche.

Biochemical premature adrenarche is defined by elevated serum DHEAS [≥40 μg/dL] before age 8 y in girls. This condition is receiving more attention due to its association with obesity, hyperinsulinemia, dyslipidemia, and polycystic ovary syndrome. Nevertheless, the link between early androgen excess and these risk factors remains unknown.

The Association of Accelerated Early Growth, Timing of Puberty, and Metabolic Consequences in Children.

Accelerated early growth and early timing of puberty or pubertal variant have been noticed as risk factors for metabolic syndrome, more frequently observed in children born small for gestational age (SGA) or children with premature adrenarche (PA). Children with SGA, especially if they make an accelerated catch-up growth in early life, carry a higher risk for long-term metabolic consequences, such as type 2 diabetes, insulin resistance, and cardiovascular diseases. Furthermore, multiple studies support that these children, either born SGA or with a history of PA, may have earlier pubertal timing, which is also associated with various metabolic risks.

New insights from GWAS on BMI-related growth traits in a longitudinal cohort of admixed children with Native American and European ancestry.

Body-mass index (BMI) is a hallmark of adiposity. In contrast with adulthood, the genetic architecture of BMI during childhood is poorly understood. The few genome-wide association studies (GWAS) on children have been performed almost exclusively in Europeans and at single ages.

Higher Prepubertal IGF-1 Concentrations Associate to Earlier Pubertal Tempo in Both Sexes.

Introduction: Pubertal onset is triggered by multiple neuroendocrine interactions. The role of prepubertal IGF-1 in this process has not been explored in both sexes. Our objective was to analyze the association of prepubertal IGF-1 concentration with age at thelarche (B2) and menarche (M) in girls and age at gonadarche (G2) in boys.

Assessment of a consensus definition of obesity and metabolic health phenotypes in children at different pubertal stages.

Not all individuals with obesity develop metabolic complications, which has brought about the concepts of metabolically healthy and unhealthy obesity (MHO/MUO). However, inconsistent definitions of these conditions have limited their understanding. We assessed whether a recently-proposed consensus definition for MHO/MUO correlates with adiposity and reflects metabolic risk parameters during puberty.

The p190 RhoGAPs, ARHGAP35, and ARHGAP5 are implicated in GnRH neuronal development: Evidence from patients with idiopathic hypogonadotropic hypogonadism, zebrafish, and in vitro GAP activity assay.

Purpose: The study aimed to identify novel genes for idiopathic hypogonadotropic hypogonadism (IHH).

Methods: A cohort of 1387 probands with IHH underwent exome sequencing and de novo, familial, and cohort-wide investigations. Functional studies were performed on 2 p190 Rho GTPase-activating proteins (p190 RhoGAP), ARHGAP35 and ARHGAP5, which involved in vivo modeling in larval zebrafish and an in vitro p190A-GAP activity assay.

Management of Growth Disorders in Puberty: GH, GnRHa, and Aromatase Inhibitors: A Clinical Review.

Pubertal children with significant growth retardation represent a considerable therapeutic challenge. In growth hormone (GH) deficiency, and in those without identifiable pathologies (idiopathic short stature), the impact of using GH is significantly hindered by the relentless tempo of bone age acceleration caused by sex steroids, limiting time available for growth. Estrogen principally modulates epiphyseal fusion in females and males.

Habitual Phytoestrogen Intake Is Associated with Breast Composition in Girls at 2 Years after Menarche Onset.

Background: High phytoestrogen intake during adolescence is associated with a reduced risk of breast cancer. Breast density (BD) is a strong predictor of breast cancer and can be considered an early marker. We aim to assess the association between the mean habitual intake of isoflavones, lignans, and total phytoestrogens intake during puberty until 2 years after menarche onset and absolute fibroglandular volume (AFGV) and percentage of fibroglandular volume (%FGV) in Hispanic girls at the end of puberty.

Novel OTX2 loss of function variant associated with congenital hypopituitarism without eye abnormalities.

Objectives: The normal development of the pituitary gland requires multiple induction signals and transcription factors encoded by more than 30 genes, including . mutations have been described with eye abnormalities and variable congenital hypopituitarism, but rarely with hypopituitarism without ocular manifestations.

Case Presentation: We report a girl with hypopituitarism associated with pituitary hypoplasia and pituitary stalk atrophy, without ocular manifestations.

Biallelic POC1A variants cause syndromic severe insulin resistance with muscle cramps.

Objective: To describe clinical, laboratory, and genetic characteristics of three unrelated cases from Chile, Portugal, and Saudi Arabia with severe insulin resistance, SOFT syndrome, and biallelic pathogenic POC1A variants.

Design: Observational study.

Methods: Probands' phenotypes, including short stature, dysmorphism, and insulin resistance, were compared with previous reports.

High DHEAS in girls and metabolic features throughout pubertal maturation.

Context: An association between premature adrenarche and metabolic syndrome at presentation has been described. Our aim was to assess whether the presence of high dehydroepiandrosterone sulphate (DHEAS [HD]) at the adrenarche determines the risk of metabolic syndrome during puberty, taking into account body mass index (BMI) and birth weight.

Design: Prospective observational.

Lack of GNAS Remethylation During Oogenesis May Be a Cause of Sporadic Pseudohypoparathyroidism Type Ib.

Context: Pseudohypoparathyroidism type Ib (PHP1B) is characterized by hypocalcemia and hyperphosphatemia due to parathyroid hormone resistance in the proximal renal tubules. Maternal pathogenic STX16/GNAS variants leading to maternal epigenetic GNAS changes impair expression of the stimulatory G protein alpha-subunit (Gsα) thereby causing autosomal dominant PHP1B. In contrast, genetic defects responsible for sporadic PHP1B (sporPHP1B) remain mostly unknown.

Genome-Wide Association Study and Polygenic Risk Scores of Serum DHEAS Levels in a Chilean Children Cohort.

Context: Adrenarche reflects the developmental growth of the adrenal zona reticularis, which produces increasing adrenal androgen secretion (eg, dehydroepiandrosterone [DHEA]/dehydroepiandrosterone sulfate [DHEAS]) from approximately age 5 to 15 years.

Objective: We hypothesized that the study of the genetic determinants associated with variations in serum DHEAS during adrenarche might detect genetic variants influencing the rate or timing of this process.

Methods: Genome-wide genotyping was performed in participants of the Chilean pediatric Growth and Obesity Chilean Cohort Study (GOCS) cohort (n = 788).

Primary Ovarian Failure in Addition to Classical Clinical Features of Coats Plus Syndrome in a Female Carrying 2 Truncating Variants of CTC1.

Coats plus syndrome is an autosomal recessive multisystemic and pleiotropic disorder affecting the eyes, brain, bone, and gastrointestinal tract, usually caused by compound heterozygous variants of the conserved telomere maintenance component 1 gene (CTC1), involved in telomere homeostasis and replication. So far, most reported patients are compound heterozygous for a truncating mutation and a missense variant. The phenotype is believed to result from telomere dysfunction, with accumulation of DNA damage, cellular senescence, and stem cell depletion.

Novel loci and Mapuche genetic ancestry are associated with pubertal growth traits in Chilean boys.

Puberty is a complex developmental process that varies considerably among individuals and populations. Genetic factors explain a large proportion of the variability of several pubertal traits. Recent genome-wide association studies (GWAS) have identified hundreds of variants involved in traits that result from body growth, like adult height.