Maria Felicia Faienza1, Mariangela Chiarito2, Giacomina Brunetti3, Gabriele D'Amato4. 1. Paediatric Unit, Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy. mariafelicia.faienza@uniba.it. 2. Paediatric Unit, Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy. 3. Department of Basic Medical Sciences, Neuroscience and Sense Organs, Section of Human Anatomy and Histology, University of Bari "A. Moro", Bari, Italy. 4. Neonatal Intensive Care Unit, Di Venere Hospital, Bari, Italy.
Abstract
PURPOSE: Short stature is a common clinical presentation, thus it is widely accepted that it is a polygenic trait. However, genome wide association and next generation sequencing studies have recently challenged this view, suggesting that many of the children classified as idiopathic short stature could instead have monogenic defects. Linear growth is determined primarily by chondrogenesis at the growth plate. This process results from chondrocyte proliferation, hypertrophy, and extracellular matrix secretion, and it is perfectly coordinated by complex networks of local paracrine and endocrine factors. Alterations in genes which control growth plate development can explain a large number of cases of isolated short stature, allowing an etiological diagnosis. METHODS/ RESULTS: We reviewed recent data on the genetic alterations in fundamental cellular processes, paracrine signaling, and cartilage matrix formation associated with impaired growth plate chondrogenesis. In particular we focused on growth plate gene involvement in nonsyndromic short stature. CONCLUSIONS: The identification of genetic basis of growth failure will have a significant impact on the care of children affected with short stature.
PURPOSE:Short stature is a common clinical presentation, thus it is widely accepted that it is a polygenic trait. However, genome wide association and next generation sequencing studies have recently challenged this view, suggesting that many of the children classified as idiopathic short stature could instead have monogenic defects. Linear growth is determined primarily by chondrogenesis at the growth plate. This process results from chondrocyte proliferation, hypertrophy, and extracellular matrix secretion, and it is perfectly coordinated by complex networks of local paracrine and endocrine factors. Alterations in genes which control growth plate development can explain a large number of cases of isolated short stature, allowing an etiological diagnosis. METHODS/ RESULTS: We reviewed recent data on the genetic alterations in fundamental cellular processes, paracrine signaling, and cartilage matrix formation associated with impaired growth plate chondrogenesis. In particular we focused on growth plate gene involvement in nonsyndromic short stature. CONCLUSIONS: The identification of genetic basis of growth failure will have a significant impact on the care of children affected with short stature.
Entities:
Keywords:
Aggrecan; Children; Gene; Growth plate; Isolated short stature; SHOX
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