A5087437417- Growth Hormone and Insulin-like Growth Factors
- Genetic Syndromes and Imprinting
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Fibroblast Growth Factor Research
- Connective tissue disorders research
- Proteoglycans and glycosaminoglycans research
- Birth, Development, and Health
- Epigenetics and DNA Methylation
- Osteoarthritis Treatment and Mechanisms
- Congenital heart defects research
- RNA Research and Splicing
- Genomics and Rare Diseases
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Lipid metabolism and disorders
- Protein Tyrosine Phosphatases
- Neonatal Respiratory Health Research
- Thyroid and Parathyroid Surgery
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Thyroid Cancer Diagnosis and Treatment
- Bone Metabolism and Diseases
- NF-κB Signaling Pathways
- Metalloenzymes and iron-sulfur proteins
- Pituitary Gland Disorders and Treatments
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2014-2024
National Institutes of Health
2011-2024
Children's National
2023-2024
George Washington University
2023-2024
Pulmonary and Allergy Associates
2021
University of Occupational and Environmental Health Japan
2021
University of North Sumatra
2019
Korea University Medical Center
2019
Yamaguchi University
2019
Eunice Kennedy Shriver Center
2016
Histone methyltransferases EZH1 and EZH2 catalyse the trimethylation of histone H3 at lysine 27 (H3K27), which serves as an epigenetic signal for chromatin condensation transcriptional repression. Genome-wide associated studies have implicated in control height mutations cause Weaver syndrome, includes skeletal overgrowth. Here we show that combined loss Ezh1 Ezh2 chondrocytes severely impairs growth mice. Both principal processes underlying plate chondrogenesis, chondrocyte proliferation...
Bones at different anatomical locations vary dramatically in size. For example, human femurs are 20-fold longer than the phalanges fingers and toes. The mechanisms responsible for these size differences poorly understood. Bone elongation occurs growth plates advances rapidly early life but then progressively slows due to a developmental program termed "growth plate senescence." This includes declines cell proliferation hypertrophy, depletion of cells all zones, extensive underlying changes...
Abstract SP7/Osterix is a transcription factor critical for osteoblast maturation and bone formation. Homozygous loss-of-function mutations in SP7 cause osteogenesis imperfecta type XII, but neomorphic (gain-of-new-function) of have not been reported humans. Here we describe de novo dominant missense variant (c.926 C > G:p.S309W) patient with craniosynostosis, cranial hyperostosis, long fragility. Histomorphometry shows increased osteoblasts decreased mineralization. Mice the...
Introduction: Variants in the intron splicing enhancer (ISE) of 3 GH1 gene are implicated etiology isolated growth hormone deficiency Type 2 (Type II IGHD). Methods: Exome sequencing was performed to screen variants that co-segregated with IGHD an extended family IGHD. The causality candidate variant assessed using bioinformatic tools and previous vitro studies. Results: identified a rare intronic (NM_000515.5, c.291+34 G>A) second XGGG repeat ISE GH1, which occurred de novo mother passed...
Growth plate chondrocytes undergo sequential differentiation to form the resting zone, proliferative zone (PZ), and hypertrophic (HZ). The important role of microRNAs (miRNAs) in growth was previously revealed by cartilage-specific ablation Dicer, an enzyme essential for biogenesis many miRNAs. To identify specific miRNAs that regulate PZ HZ chondrocytes, we microdissected individual zones from juvenile rats performed miRNA profiling using a solution hybridization method sequencing....
Aggrecan, a proteoglycan, is an important component of cartilage extracellular matrix, including that the growth plate. Heterozygous mutations in ACAN, gene encoding aggrecan, cause autosomal dominant short stature, accelerated skeletal maturation, and joint disease. The inheritance pattern presence bone age equal to or greater than chronological have been consistent features, serving as diagnostic clues. From family 1, 6-year-old boy presented with stature [height standard deviation score...
Overgrowth syndromes can be caused by pathogenic genetic variants in epigenetic writers, such as DNA and histone methyltransferases. However, no overgrowth disorder has previously been ascribed to a gene that acts primarily an reader. Here, we studied male individual with generalized of prenatal onset. Exome sequencing identified hemizygous frameshift variant Spindlin 4 (SPIN4), X-linked inheritance. We found evidence SPIN4 binds specific modifications, promotes canonical WNT signaling,...
Mutations in the genes encoding for GHRH receptor (GHRHR) and GH (GH1) are most common cause of familial isolated deficiency (IGHD). GHRHR mutations often associated with anterior pituitary hypoplasia (APH), but this has been reported almost exclusively children older than 8 yr. We analyzed measured size a consanguineous family father three five siblings IGHD.The aim study was to find mutated gene severe IGHD.We sequenced whole coding regions intron-exon boundaries from peripheral DNA index...
Abstract We report a case of persistent gynecomastia in healthy 20-year-old man after 1 month low-dose finasteride. Finasteride was discontinued 2 months, and unchanged 5 months drug withdrawal. The regressed but did not resolve 6 treatment with raloxifene, selective estrogen receptor modulator. One year later, bilateral mammoplasty performed to remove the remaining breast tissue. Finasteride, 5-alpha-reductase inhibitor, is widely used for androgenetic alopecia. Gynecomastia an expected...
Linear growth occurs at the plate. Therefore, genetic defects that interfere with normal function of plate can cause linear disorders. Many causes disorders have already been identified in humans. However, recent genome-wide approaches broadened our knowledge mechanisms growth, not only providing novel monogenic but also revealing single nucleotide polymorphisms genes affect height general population. The as causative are heterogeneous, playing a role various growth-regulating including...
Summary Context The primary preoperative method for distinguishing malignant from benign thyroid nodules is fine‐needle aspiration ( FNA ) cytology, but it frequently inconclusive. Midkine MDK a heparin‐binding growth factor, which overexpressed in papillary carcinoma PTC ). Objective We measured concentrations samples and to explore the possibility that measurement might aid evaluation of nodules. Design 35 subjects underwent 45 nodules, followed by thyroidectomy, providing histological...
Congenital hypopituitarism usually occurs sporadically. In most patients, the etiology remains unknown.We studied 13 children with sporadic congenital hypopituitarism. Children non-endocrine, non-familial idiopathic short stature (NFSS) (n = 19) served as a control group. Exome sequencing was performed in probands and both unaffected parents. A burden testing approach used to compare number of candidate variants two groups.First, we assessed frequency rare, predicted-pathogenic 42 genes...
In many children with short stature, the etiology of decreased linear growth remains unknown. We sought to identify underlying genetic in a patient irregular plates proximal phalanges, developmental delay, and mildly dysmorphic facial features. Exome sequencing identified de novo, heterozygous, nonsense mutation (c.1606C>T:p.R536X) QRICH1 . vitro studies confirmed that impaired expression protein. SiRNA‐mediated knockdown Qrich1 primary mouse epiphyseal chondrocytes caused downregulation...
Thyroid nodules are common, and approximately 5% of these malignant. Pleiotrophin (PTN) is a heparin-binding growth factor which overexpressed in many cancers. The expression PTN papillary thyroid cancer (PTC) unknown.74 subjects (age 47 ± 12 y, 15 males) who had thyroidectomy with histological diagnosis: 79 benign 23 PTCs (10 classic, 6 tall cell, follicular variant 1 undetermined). Fine-needle aspiration (FNA) samples were obtained ex vivo from surgically excised tissue assayed for...
Background Midkine (MDK) and pleiotrophin (PTN) are heparin-binding growth factors that, in rodents, highly expressed early life decrease to undetectable levels by adulthood. The potential roles of MDK PTN human development not completely elucidated. Method Findings To delineate the role development, we developed high sensitivity assays measure their concentrations amniotic fluid (AF) at various gestational ages both healthy complicated pregnancies. We found that these could be readily...