Tendon-associated gene expression precedes osteogenesis in mid-palatal suture establishment.

Orthodontic maxillary expansion relies on intrinsic mid-palatal suture mechanobiology to induce guided osteogenesis, yet establishment of the mid-palatal suture within the continuous secondary palate and causes of maxillary insufficiency remain poorly understood. In contrast, advances in cranial suture research hold promise to improve surgical repair of prematurely fused cranial sutures in craniosynostosis to potentially restore the obliterated signaling environment and ensure continual success of the intervention. We hypothesized that mid-palatal suture establishment is governed by shared principles with calvarial sutures and involves functional linkage between expanding primary ossification centres with the midline mesenchyme.

Spatial Transcriptomic Analysis of Pituitary Corticotroph Tumors.

Context: Spatial transcriptomic (ST) analysis of tumors provides a novel approach to studying gene expression along with the localization of tumor cells in their environment to uncover spatial interactions.

Design: We present ST analysis of corticotroph pituitary neuroendocrine tumors (PitNETs) from formalin-fixed, paraffin-embedded tissues. ST data were compared to immunohistochemistry results.

The spectrum of growth hormone excess in Carney complex and genotype-phenotype correlations.

Context: Carney complex (CNC) is a familial neoplasia syndrome associated with growth hormone (GH) excess (GHE).

Objective: To describe the frequency of GHE in a large cohort of patients with CNC, and to identify genotype-phenotype correlations.

Methods: Patients with CNC with at least one biochemical evaluation of GH secretion at our center from 1995-2021 (n=140) were included in the study.

Evidence of the Role of Inflammation and the Hormonal Environment in the Pathogenesis of Adrenal Myelolipomas in Congenital Adrenal Hyperplasia.

Adrenal myelolipomas (AML) are composed of mature adipose and hematopoietic components. They represent approximately 3 percent of adrenal tumors and are commonly found in patients with congenital adrenal hyperplasia (CAH). CAH provides a unique environment to explore AML pathogenesis.

Profiles of Wnt pathway gene expression during tooth morphogenesis.

Mouse and human genetic studies indicate key roles of the ligand in odontogenesis. Previous studies have identified effectors and regulators of the Wnt signaling pathway actively expressed during key stages of tooth morphogenesis. However, limitations in multiplexing and spatial resolution hindered a more comprehensive analysis of these signaling molecules.

Paediatric Cushing syndrome: a prospective, multisite, observational cohort study.

Background: Paediatric endogenous Cushing syndrome is a rare condition with variable signs and symptoms of presentation. We studied a large cohort of paediatric patients with endogenous Cushing syndrome with the aim of describing anthropometric, clinical, and biochemical characteristics as well as associated complications and outcomes to aid diagnosis, treatment, and management.

Methods: In this prospective, multisite cohort study, we studied children and adolescents (≤18 years at time of presentation) with a diagnosis of Cushing syndrome.

FAF1 Gene Involvement in Pituitary Corticotroph Tumors.

Cushing's disease (CD) is caused by rare pituitary corticotroph tumors that lead to corticotropin (ACTH) excess. Variants in , a pro-apoptotic protein involved in FAS-induced cell death, have been implicated in malignant disorders but the involvement of in pituitary tumors has not been studied. Genetic data from patients with CD were reviewed for variants in gene.

High-frequency variants in PKA signaling-related genes within a large pediatric cohort with obesity or metabolic abnormalities.

Introduction: Pediatric obesity has steadily increased in recent decades. Large-scale genome-wide association studies (GWAS) conducted primarily in Eurocentric adult populations have identified approximately 100 loci that predispose to obesity and type II diabetes. GWAS in children and individuals of non-European descent, both disproportionately affected by obesity, are fewer.

Multimodal spatiotemporal transcriptomic resolution of embryonic palate osteogenesis.

The terminal differentiation of osteoblasts and subsequent formation of bone marks an important phase in palate development that leads to the separation of the oral and nasal cavities. While the morphogenetic events preceding palatal osteogenesis are well explored, major gaps remain in our understanding of the molecular mechanisms driving the formation of this bony union of the fusing palate. Through bulk, single-nucleus, and spatially resolved RNA-sequencing analyses of the developing secondary palate, we identify a shift in transcriptional programming between embryonic days 14.

Embryonic stem cell factor FOXD3 (Genesis) defects in gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms, believed to originate from the interstitial cells of Cajal (ICC), often caused by overexpression of tyrosine kinase receptors (TKR) KIT or PDGFRA. Here, we present evidence that the embryonic stem cell factor FOXD3, first identified as 'Genesis' and involved in both gastrointestinal and neural crest cell development, is implicated in GIST pathogenesis; its involvement is investigated both in vitro and in zebrafish and a mouse model of FOXD3 deficiency. Samples from a total of 58 patients with wild-type GISTs were used for molecular analyses, including Sanger sequencing, comparative genomic hybridization, and methylation analysis.

Germline loss-of-function variants are enriched in subjects with pituitary hypersecretion.

Introduction: Pituitary adenomas (PAs) are common, usually benign tumors of the anterior pituitary gland which, for the most part, have no known genetic cause. PAs are associated with major clinical effects due to hormonal dysregulation and tumoral impingement on vital brain structures. PAM encodes a multifunctional protein responsible for the essential C-terminal amidation of secreted peptides.

Integrated spatiotemporal transcriptomic resolution of embryonic palate osteogenesis.

The differentiation of osteoblasts and the subsequent formation of bone marks an important terminal phase in palate formation that leads to the separation of the oral and nasal cavities. While the developmental events that precede palatal osteogenesis are well explored, major gaps remain in our understanding of the molecular mechanisms that lead to the bony union of fusing palatal shelves. Herein, the timeline of osteogenic transcriptional programming is unveiled in the embryonic palate by way of integrated bulk, single-cell, and spatially resolved RNA-seq analyses.

Spatial Multiomics Reveal the Role of Wnt Modulator, Dkk2, in Palatogenesis.

Multiple genetic and environmental etiologies contribute to the pathogenesis of cleft palate, which constitutes the most common among the inherited disorders of the craniofacial complex. Insights into the molecular mechanisms regulating osteogenic differentiation and patterning in the palate during embryogenesis are limited and needed for the development of innovative diagnostics and cures. This study utilized the mouse model with a consistent phenotype of cleft secondary palate to investigate the role of in the process of palatal osteogenesis.

Congenital adrenal hyperplasia due to two rare CYP21A2 variant alleles, including a novel attenuated CYP21A1P/CYP21A2 chimera.

Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21OH) deficiency is an autosomal recessive inborn error of cortisol biosynthesis, with varying degrees of aldosterone production. There is a continuum of phenotypes which generally correlate with genotype and the expected residual 21OH activity of the less severely impaired allele. CYP21A1P/CYP21A2 chimeric genes caused by recombination between CYP21A2 and its highly homologous CYP21A1P pseudogene are common in CAH and typically associated with salt-wasting CAH, the most severe form.

Exploratory Study of the Association of Genetic Factors With Recovery of Adrenal Function in Cushing Disease.

Successful treatment of endogenous Cushing disease (CD) is often followed by a period of adrenal insufficiency (AI). We performed an exploratory study on genetic factors potentially involved in the hypothalamic-pituitary-adrenal (HPA) axis recovery in patients with CD after remission. We identified 90 patients who achieved remission after surgery and had a minimum of 3 months follow-up.

Molecular tools for diagnosing diseases of the adrenal cortex.

Purpose Of Review: The adrenal glands produce some of the most essential for life hormones, including cortisol and other steroids, and catecholamines. The former is produced from the adrenal cortex, whereas the latter is from the medulla. The two parts are anatomically and functionally distinct and it would be impossible in the context of one short article to cover all molecular updates on both the cortex and the medulla.

miRNA Expression Profiles of Mouse Round Spermatids in GRTH/DDX25-Mediated Spermiogenesis: mRNA-miRNA Network Analysis.

GRTH/DDX25 is a testis-specific DEAD-box family of RNA helicase, which plays an essential role in spermatogenesis and male fertility. There are two forms of GRTH, a 56 kDa non-phosphorylated form and a 61 kDa phosphorylated form (pGRTH). GRTH-KO and GRTH Knock-In (KI) mice with R242H mutation (lack pGRTH) are sterile with a spermatogenic arrest at step 8 of spermiogenesis due to failure of round spermatids (RS) to elongate.

Pseudogene Variants May Interfere with the Genetic Testing of CAH-X.

CAH-X is a hypermobility-type Ehlers-Danlos syndrome connective tissue dysplasia affecting approximately 15% of patients with 21-hydroxylase deficiency (21-OHD) congenital adrenal hyperplasia (CAH) due to contiguous deletion of and genes. The two most common genetic causes of CAH-X are chimeras with pseudogene substitution for exons 35-44 (CAH-X CH-1) and exons 40-44 (CAH-X CH-2). A total of 45 subjects (40 families) from a cohort of 278 subjects (135 families of 21-OHD and 11 families of other conditions) were found to have excessive exon 40 copy number as measured by digital PCR.

Genetic drivers of Cushing's disease: Frequency and associated phenotypes.

Purpose: Cushing's disease (CD) is often explained by a single somatic sequence change. Germline defects, however, often go unrecognized. We aimed to determine the frequency and associated phenotypes of genetic drivers of CD in a large cohort.

Disorders of the adrenal cortex: Genetic and molecular aspects.

Adrenal cortex produces glucocorticoids, mineralocorticoids and adrenal androgens which are essential for life, supporting balance, immune response and sexual maturation. Adrenocortical tumors and hyperplasias are a heterogenous group of adrenal disorders and they can be either sporadic or familial. Adrenocortical cancer is a rare and aggressive malignancy, and it is associated with poor prognosis.