Genetic factors play a crucial role in determining human height. Short stature commonly affects multiple family members and therefore, familial short stature (FSS) represents a significant proportion of growth disorders. Traditionally, FSS was considered a benign polygenic condition representing a subcategory of idiopathic short stature (ISS). However, advancements in genetic research have revealed that FSS can also be monogenic, inherited in an autosomal dominant manner and can result from different mechanisms including primary growth plate disorders, growth hormone deficiency/insensitivity or by the disruption of fundamental intracellular pathways. These discoveries have highlighted a broader phenotypic spectrum for monogenic forms of short stature, which may exhibit mild manifestations indistinguishable from ISS. Given the overlapping features and the difficulty in differentiating polygenic from monogenic FSS without genetic testing, some researchers redefine FSS as a descriptive term that encompasses any familial occurrence of short stature, regardless of the underlying cause. This shift emphasizes the complexity of diagnosing and managing short stature within families, reflecting the diverse genetic landscape that influences human growth.

• Keywords
• autosomal dominant short stature, familial short stature, genetics, growth plate, short stature,
• MeSH
• Phenotype MeSH
• Humans MeSH
• Dwarfism genetics   MeSH
• Growth Disorders * genetics   MeSH
• Body Height * genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

In-cell profiling enables the evaluation of receptor tyrosine activity in a complex environment of regulatory networks that affect signal initiation, propagation and feedback. We used FGF-receptor signaling to identify EGR1 as a locus that strongly responds to the activation of a majority of the recognized protein kinase oncogenes, including 30 receptor tyrosine kinases and 154 of their disease-associated mutants. The EGR1 promoter was engineered to enhance trans-activation capacity and optimized for simple screening assays with luciferase or fluorescent reporters. The efficacy of the developed, fully synthetic reporters was demonstrated by the identification of novel targets for two clinically used tyrosine kinase inhibitors, nilotinib and osimertinib. A universal reporter system for in-cell protein kinase profiling will facilitate repurposing of existing anti-cancer drugs and identification of novel inhibitors in high-throughput screening studies.

• Keywords
• activity, cancer biology, cell biology, human, in cell, mouse, profiling, protein kinase, receptor tyrosine kinase, reporter,
• MeSH
• Cell Line MeSH
• Cytological Techniques methods   MeSH
• Intravital Microscopy MeSH
• Humans MeSH
• Mice MeSH
• Oncogene Proteins analysis   MeSH
• Optical Imaging MeSH
• Protein Kinases analysis   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Oncogene Proteins MeSH
• Protein Kinases MeSH