Primary cilium projects from cells to provide a communication platform with neighboring cells and the surrounding environment. This is ensured by the selective entry of membrane receptors and signaling molecules, producing fine-tuned and effective responses to the extracellular cues. In this study, we focused on one family of signaling molecules, the fibroblast growth factor receptors (FGFRs), their residence within cilia, and its role in FGFR signaling. We show that FGFR1 and FGFR2, but not FGFR3 and FGFR4, localize to primary cilia of the developing mouse tissues and in vitro cells. For FGFR2, we demonstrate that the ciliary residence is necessary for its signaling and expression of target morphogenic genes. We also show that the pathogenic FGFR2 variants have minimal cilium presence, which can be rescued for the p.P253R variant associated with the Apert syndrome by using the RLY-4008 kinase inhibitor. Finally, we determine the molecular regulators of FGFR2 trafficking to cilia, including IFT144, BBS1, and the conserved T429V430 motif within FGFR2.

• MeSH
• cilie * metabolismus   genetika   MeSH
• epitelové buňky * metabolismus   MeSH
• lidé MeSH
• myši MeSH
• receptor fibroblastových růstových faktorů, typ 1 metabolismus   genetika   MeSH
• receptor fibroblastových růstových faktorů, typ 2 * metabolismus   genetika   MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• FGFR2 protein, human MeSH Prohlížeč
• Fgfr2 protein, mouse MeSH Prohlížeč
• receptor fibroblastových růstových faktorů, typ 1 MeSH
• receptor fibroblastových růstových faktorů, typ 2 * MeSH

Although the detection of several components of the fibroblast growth factor (FGF) signaling pathway in human embryonic stem cells (hESCs) has been reported, the functionality of that pathway and effects on cell fate decisions are yet to be established. In this study we characterized expression of FGF-2, the prototypic member of the FGF family, and its receptors (FGFRs) in undifferentiated and differentiating hESCs; subsequently, we analyzed the effects of FGF-2 on hESCs, acting as both exogenous and endogenous factors. We have determined that undifferentiated hESCs are abundant in several molecular-mass isoforms of FGF-2 and that expression pattern of these isoforms remains unchanged under conditions that induce hESC differentiation. Significantly, FGF-2 is released by hESCs into the medium, suggesting an autocrine activity. Expression of FGFRs in undifferentiated hESCs follows a specific pattern, with FGFR1 being the most abundant species and other receptors showing lower expression in the following order: FGFR1 --> FGFR3 --> FGFR4 --> FGFR2. Initiation of differentiation is accompanied by profound changes in FGFR expression, particularly the upregulation of FGFR1. When hESCs are exposed to exogenous FGF-2, extracellular signal-regulated kinases are phosphorylated and thereby activated. However, the presence or absence of exogenous FGF-2 does not significantly affect the proliferation of hESCs. Instead, increased concentration of exogenous FGF-2 leads to reduced outgrowth of hESC colonies with time in culture. Finally, the inhibitor of FGFRs, SU5402, was used to ascertain whether FGF-2 that is released by hESCs exerts its activities via autocrine pathways. Strikingly, the resultant inhibition of FGFR suppresses activation of downstream protein kinases and causes rapid cell differentiation, suggesting an involvement of autocrine FGF signals in the maintenance of proliferating hESCs in the undifferentiated state. In conclusion from our data, we propose that this endogenous FGF signaling pathway can be implicated in self-renewal or differentiation of hESCs.

• MeSH
• buněčná diferenciace MeSH
• embryo savčí cytologie   MeSH
• fibroblastový růstový faktor 2 biosyntéza   fyziologie   MeSH
• fosforylace MeSH
• kmenové buňky cytologie   účinky léků   metabolismus   MeSH
• lidé MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• protein - isoformy MeSH
• pyrroly farmakologie   MeSH
• receptor fibroblastových růstových faktorů, typ 2 biosyntéza   fyziologie   MeSH
• receptory fibroblastových růstových faktorů biosyntéza   fyziologie   MeSH
• signální transdukce fyziologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• FGFR2 protein, human MeSH Prohlížeč
• fibroblastový růstový faktor 2 MeSH
• mitogenem aktivované proteinkinasy MeSH
• protein - isoformy MeSH
• pyrroly MeSH
• receptor fibroblastových růstových faktorů, typ 2 MeSH
• receptory fibroblastových růstových faktorů MeSH
• SU 5402 MeSH Prohlížeč

PURPOSE: Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) protein overexpression is an emerging biomarker in gastric cancer and gastroesophageal junction cancer (GC). We assessed FGFR2b protein overexpression prevalence in nearly 3,800 tumor samples as part of the prescreening process for a global phase III study in patients with newly diagnosed advanced or metastatic GC. METHODS: As of June 28, 2024, 3,782 tumor samples from prescreened patients from 37 countries for the phase III FORTITUDE-101 trial (ClinicalTrials.gov identifier: NCT05052801) were centrally tested for FGFR2b protein overexpression by immunohistochemistry (IHC) and had evaluable results. FGFR2b positivity was defined as both any % tumor cells (TC) and ≥10% TC exhibiting moderate-to-strong (2+/3+) membranous FGFR2b staining. Prevalence was analyzed across patient and sample characteristics. RESULTS: FGFR2b protein overexpression at any % and ≥10%, 2+/3+ TC positivity was 37.8% (1,428/3,782 [95% CI, 36.2 to 39.3]) and 16.2% (612/3,782 [95% CI, 15 to 17.4]), respectively. Of any %, 2+/3+ TC-positive tumors, 42.9% (612/1,428 [95% CI, 40.3 to 45.4]) were FGFR2b ≥10%, 2+/3+ TC positive. FGFR2b prevalence was not notably different within multiple patient and sample characteristics examined (age, sex, collection method [biopsy v resection], collection site, location of primary tumor, and geographic region). CONCLUSION: As of the data cutoff date, we report the largest prevalence assessment of FGFR2b protein overexpression in GC with more than one third (37.8%) of patients with GC exhibiting FGFR2b protein overexpression (any % TC, 2+/3+) by a validated IHC assay. Approximately 16% of patients had FGFR2b protein overexpression in ≥10% of TC. FGFR2b prevalence was similar across geographic regions and within defined patient and sample variables regardless of the level of expression.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery MeSH
• nádory žaludku * patologie   metabolismus   MeSH
• prevalence MeSH
• receptor fibroblastových růstových faktorů, typ 2 * metabolismus   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• Názvy látek
• FGFR2 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• receptor fibroblastových růstových faktorů, typ 2 * MeSH

The transcription program that is responsible for the pluripotency of human ESCs (hESCs) is believed to be comaintained by exogenous fibroblast growth factor-2 (FGF-2), which activates FGF receptors (FGFRs) and stimulates the mitogen-activated protein kinase (MAPK) pathway. However, the same pathway is stimulated by insulin receptors, insulin-like growth factor 1 receptors, and epidermal growth factor receptors. This mechanism is further complicated by intracrine FGF signals. Thus, the molecular mechanisms by which FGF-2 promotes the undifferentiated growth of hESCs are unclear. Here we show that, in undifferentiated hESCs, exogenous FGF-2 stimulated the expression of stem cell genes while suppressing cell death and apoptosis genes. Inhibition of autocrine FGF signaling caused upregulation of differentiation-related genes and downregulation of stem cell genes. Thus, exogenous FGF-2 reinforced the pluripotency maintenance program of intracrine FGF-2 signaling. Consistent with this hypothesis, expression of endogenous FGF-2 decreased during hESC differentiation and FGF-2 knockdown-induced hESC differentiation. In addition, FGF-2 signaling via FGFR2 activated MAPK kinase/extracellular signal-regulated kinase and AKT kinases, protected hESC from stress-induced cell death, and increased hESC adhesion and cloning efficiency. This stimulation of self-renewal, cell survival, and adhesion by exogenous and endogenous FGF-2 may synergize to maintain the undifferentiated growth of hESCs.

• MeSH
• aktivace enzymů MeSH
• buněčná adheze účinky léků   fyziologie   MeSH
• buněčná diferenciace účinky léků   fyziologie   MeSH
• buněčné linie MeSH
• buňky - růstové procesy účinky léků   fyziologie   MeSH
• down regulace MeSH
• embryonální kmenové buňky cytologie   účinky léků   metabolismus   MeSH
• exprese genu MeSH
• fibroblastový růstový faktor 2 genetika   metabolismus   farmakologie   MeSH
• fosforylace MeSH
• imunoblotting MeSH
• lidé MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• onkogenní protein v-akt metabolismus   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• receptor fibroblastových růstových faktorů, typ 2 metabolismus   MeSH
• signální transdukce MeSH
• viabilita buněk účinky léků   fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fibroblastový růstový faktor 2 MeSH
• mitogenem aktivované proteinkinasy MeSH
• onkogenní protein v-akt MeSH
• receptor fibroblastových růstových faktorů, typ 2 MeSH

OBJECTIVES: Morphological changes of blood vessel wall have been described in placenta from pregnancies complicated by diabetes mellitus type-I. STUDY DESIGN: We measured mRNA expression of vascular endothelial growth factor (VEGF), angiopoietin 1 and 2 (Ang-1 and Ang-2), their receptors VEGFR-1, VEGFR-2, Tie-2, fibroblast growth factor 2 (FGF-2), and its receptor FGF-2R in placental tissue of diabetes type-I patients, in normal term placenta, and endometrium of non-pregnant women by real time reverse transcriptase PCR. RESULTS: The expression of Ang-2 and VEGFR-1 mRNAs was significantly higher in placenta (P

• MeSH
• angiopoetin-1 genetika   MeSH
• angiopoetin-2 genetika   MeSH
• angiopoetiny genetika   MeSH
• diabetes mellitus 1. typu metabolismus   MeSH
• exprese genu * MeSH
• fibroblastový růstový faktor 2 genetika   MeSH
• lidé MeSH
• messenger RNA analýza   MeSH
• placenta chemie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• receptor 1 pro vaskulární endoteliální růstový faktor genetika   MeSH
• receptor 2 pro vaskulární endoteliální růstový faktor genetika   MeSH
• receptor fibroblastových růstových faktorů, typ 2 MeSH
• receptor TIE-2 genetika   MeSH
• receptory fibroblastových růstových faktorů genetika   MeSH
• těhotenství při diabetu metabolismus   MeSH
• těhotenství MeSH
• tyrosinkinasové receptory genetika   MeSH
• vaskulární endoteliální růstový faktor A genetika   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• angiopoetin-1 MeSH
• angiopoetin-2 MeSH
• angiopoetiny MeSH
• ANGPT1 protein, human MeSH Prohlížeč
• FGFR2 protein, human MeSH Prohlížeč
• fibroblastový růstový faktor 2 MeSH
• messenger RNA MeSH
• receptor 1 pro vaskulární endoteliální růstový faktor MeSH
• receptor 2 pro vaskulární endoteliální růstový faktor MeSH
• receptor fibroblastových růstových faktorů, typ 2 MeSH
• receptor TIE-2 MeSH
• receptory fibroblastových růstových faktorů MeSH
• tyrosinkinasové receptory MeSH
• vaskulární endoteliální růstový faktor A MeSH

INTRODUCTION: Search for new prognostic markers in order to improve prognostic accuracy and predict clinical outcome at the time of dia-gnosis has recently become one of the major trends in chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS, AIM OF STUDY: The aim of our study was assessment of selected markers of apoptosis and angiogenesis and their potential as new prognostic factors. We evaluated serum levels of tumor necrosis factor α (TNFα) and transforming growth factor β 1 (TGFβ1) using commercially available enzyme linked immunosorbent assay; furthermore, we quantified expression of type II receptor for transforming growth factor beta (TGFβRII) and type 2 receptor for fibroblast growth factor 2 (FGFR2) on CLL cells using flow cytometry analysis in 75 previously untreated patients with CLL (47 males and 28 females, median age, 65 years, range 38- 82) and healthy donors. RESULTS: We found significantly elevated TNFα in patients with CLL compared to the control group (p < 0.0001); high expression of TNFα was associated with unfavourable prognosis: significantly higher concentrations were found in patients with Rai highrisk group compared to low and intermediate-risk group (p = 0.0008 and p = 0.0097), with high serum β2- microglobulin (p = 0.045), massive lymphadenopathy (p = 0.0083), unmutated genes for variable region of immunoglobulin heavy chain (IgVH) (p = 0.041) and unfavourable cytogenetic aberrations (p = 0.0014). In addition, patients with progressive CLL had significantly higher TNFα than those with stable clinical course (p = 0.0009); time to treatment was significantly shorter in patients with higher TNFα (p = 0.0049). Higher TGFβ1 concentrations were associated with favourable subgroups: with Rai low risk group compared to high risk group (p = 0.011), patients without massive lymphadenopathy (p = 0.041), patients with mutated IgVH (p = 0.012) and ZAP 70 negativity (zeta associated protein of 70 kilodaltons) (p = 0.044). Patients with progressive CLL had significantly lower TGFβ1 levels than those with stable course (p = 0.0014) and time to treatment was significantly longer in patients with higher TGFβ1 (p = 0.016). Patients with Rai high risk group had significantly lower TGFβRII expression than those with low risk group (p = 0.022). The prognostic significance of FGFR2 was not found. Significant and independent prognostic factors for overall survival were high serum concentrations of TNFα and massive lymphadenopathy (p = 0.036, resp. p = 0.047). CONCLUSION: Based on our results, TNFα and TGFβ1 possess prognostic significance in CLL; further research in this direction may also be important therapeutically, because these signal pathways could serve as possible treatment targets.

• MeSH
• apoptóza fyziologie   MeSH
• chronická lymfatická leukemie krev   farmakoterapie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery krev   MeSH
• patologická angiogeneze krev   MeSH
• prognóza MeSH
• progrese nemoci MeSH
• protein-serin-threoninkinasy krev   MeSH
• protein-tyrosinkináza ZAP-70 MeSH
• průtoková cytometrie MeSH
• receptor fibroblastových růstových faktorů, typ 2 krev   MeSH
• receptory transformujícího růstového faktoru beta krev   MeSH
• referenční hodnoty MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• těžké řetězce imunoglobulinů MeSH
• TGF-beta receptor II. typu MeSH
• TNF-alfa krev   MeSH
• transformující růstový faktor beta1 krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• FGFR2 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• protein-serin-threoninkinasy MeSH
• protein-tyrosinkináza ZAP-70 MeSH
• receptor fibroblastových růstových faktorů, typ 2 MeSH
• receptory transformujícího růstového faktoru beta MeSH
• těžké řetězce imunoglobulinů MeSH
• TGF-beta receptor II. typu MeSH
• TNF-alfa MeSH
• transformující růstový faktor beta1 MeSH
• ZAP70 protein, human MeSH Prohlížeč

Antley-Bixler syndrome (ABS) is a rare congenital disorder characterized by numerous craniofacial, skeletal and, in some cases, urogenital abnormalities resulting from disordered steroidogenesis. Known genetic causes in sporadic cases of ABS include dominant mutations in the fibroblast growth factor 2 receptor gene (FGFR2). Recent research shows surprisingly that symptoms of Antley-Bixler syndrome, combined with disordered steroidogenesis and urogenital anomalies, are caused by mutations in the POR gene that encodes NADPH-cytochrome P450 oxidoreductase (CYPOR). CYPOR is a four domain-containing monomeric flavoprotein that contains two flavins, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), a binding site for NADPH, and the N-terminal sequence of 25 amino acids which determines the microsomal localization of the protein. CYPOR is the electron donor to microsomally localized cytochromes P450 that participate in xenobiotic metabolism and steroidogenesis. Mutations in the POR gene lead to apparent diminished activity of some P450 enzymes. Association of CYPOR with ABS discloses new facts about this disease and recent research shows that patients with ABS-like skeletal anomalies, but with mutations in the POR gene and disordered steroidogenesis, represent a new disorder called POR deficiency.

• MeSH
• lidé MeSH
• mnohočetné abnormality diagnóza   MeSH
• mutace * MeSH
• NADPH-cytochrom c-reduktasa nedostatek   genetika   MeSH
• receptor fibroblastových růstových faktorů, typ 2 genetika   MeSH
• syndrom MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• NADPH-cytochrom c-reduktasa MeSH
• receptor fibroblastových růstových faktorů, typ 2 MeSH

BACKGROUND/AIM: Gliomas are primary malignancies of the central nervous system (CNS). High-grade gliomas are associated with poor prognosis and modest survival rates despite intensive multimodal treatment strategies. Targeting gene fusions is an emerging therapeutic approach for gliomas that allows application of personalized medicine principles. The aim of this study was to identify detectable fusion oncogenes that could serve as predictors of currently available or newly developed targeted therapeutics in cross-sectional samples from glioma patients using next-generation sequencing (NGS). PATIENTS AND METHODS: A total of 637 patients with glial and glioneuronal tumours of the CNS who underwent tumour resection between 2017 and 2020 were enrolled. Detection of fusion transcripts in FFPE tumour tissue was performed by a TruSight Tumour 170 assay and two FusionPlex kits, Solid Tumour and Comprehensive Thyroid and Lung. RESULTS: Oncogene fusions were identified in 33 patients. The most common fusion was the KIAA1549-BRAF fusion, detected in 13 patients, followed by FGFR fusions (FGFR1-TACC1, FGFR2-CTNNA3, FGFR3-TACC3, FGFR3-CKAP5, FGFR3-AMBRA1), identified in 10 patients. Other oncogene fusions were also infrequently diagnosed, including MET fusions (SRPK2-MET and PTPRZ1-MET) in 2 patients, C11orf95-RELA fusions in 2 patients, EGFR-SEPT14 fusion in 2 patients, and individual cases of SRGAP3-BRAF, RAF1-TRIM2, EWSR1-PALGL1 and TERT-ALK fusions. CONCLUSION: The introduction of NGS techniques provides additional information about tumour molecular alterations that can aid the multimodal management of glioma patients. Patients with gliomas positive for particular targetable gene fusions may benefit from experimental therapeutics, enhancing their quality of life and prolonging survival rates.

• Klíčová slova
• Glioma, gene fusion, molecular genetics, next-generation sequencing, targeted therapy,
• MeSH
• adaptorové proteiny signální transdukční genetika   MeSH
• gliom * genetika   patologie   MeSH
• kvalita života MeSH
• lidé MeSH
• onkogenní fúze * MeSH
• onkogeny genetika   MeSH
• protein-serin-threoninkinasy MeSH
• proteiny asociované s mikrotubuly genetika   MeSH
• průřezové studie MeSH
• tyrosinfosfatasy receptorového typu, třída 5 genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adaptorové proteiny signální transdukční MeSH
• AMBRA1 protein, human MeSH Prohlížeč
• protein-serin-threoninkinasy MeSH
• proteiny asociované s mikrotubuly MeSH
• PTPRZ1 protein, human MeSH Prohlížeč
• SRPK2 protein, human MeSH Prohlížeč
• TACC3 protein, human MeSH Prohlížeč
• tyrosinfosfatasy receptorového typu, třída 5 MeSH

This is the first histological and molecular analysis of two chondrosarcomas with target-like chondrocytes that were compared with a group of conventional chondrosarcomas and enchondromas. The unique histological feature of target-like chondrocytes is the presence of unusual hypertrophic eosinophilic APAS-positive perichondrocytic rings (baskets). In the sections stained with Safranin O/Fast green, the outer part of the ring was blue and the material in the lacunar space stained orange, similarly to intercellular regions. Immunohistochemical examination showed strong positivity for vimentin, factor XIIIa, cyclin D1, osteonectin, B-cell lymphoma 2 apoptosis regulator (Bcl-2), p53 and p16. The S-100 protein was positive in 25 % of neoplastic cells. Antibodies against GFAP, D2-40 (podoplanin), CD99, CKAE1.3 and CD10 exhibited weak focal positivity. Pericellular rings/baskets contained type VI collagen in their peripheral part, in contrast to the type II collagen in intercellular interterritorial spaces. Ultrastructural examination revealed that pericellular rings contained an intralacunar component composed of microfibrils with abundant admixture of aggregates of dense amorphous non-fibrillar material. The outer extralacunar zone was made up of a layer of condensed thin collagen fibrils with admixture of non-fibrillar dense material. NGS sequencing identified a fusion transcript involving fibronectin 1 (FN1) and fibroblast growth factor receptor 2 (FGFR2) at the RNA level. At the DNA level, no significant variant was revealed except for the presumably germline variant in the SPTA1 gene.

• MeSH
• chondrocyty chemie   patologie   ultrastruktura   MeSH
• chondrosarkom * chemie   diagnóza   patologie   MeSH
• extracelulární matrix chemie   metabolismus   ultrastruktura   MeSH
• imunohistochemie MeSH
• lidé MeSH
• nádory kostí * diagnóza   metabolismus   MeSH
• proteiny S100 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• proteiny S100 MeSH

INTRODUCTION: Among children born small for gestational age, 10-15% fail to catch up and remain short (SGA-SS). The underlying mechanisms are mostly unknown. We aimed to decipher genetic aetiologies of SGA-SS within a large single-centre cohort. METHODS: Out of 820 patients treated with growth hormone (GH), 256 were classified as SGA-SS (birth length and/or birth weight <-2 SD for gestational age and life-minimum height <-2.5 SD). Those with the DNA triplet available (child and both parents) were included in the study (176/256). Targeted testing (karyotype/FISH/MLPA/specific Sanger sequencing) was performed if a specific genetic disorder was clinically suggestive. All remaining patients underwent MS-MLPA to identify Silver-Russell syndrome, and those with unknown genetic aetiology were subsequently examined using whole-exome sequencing or targeted panel of 398 growth-related genes. Genetic variants were classified using ACMG guidelines. RESULTS: The genetic aetiology was elucidated in 74/176 (42%) children. Of these, 12/74 (16%) had pathogenic or likely pathogenic (P/LP) gene variants affecting pituitary development (LHX4, OTX2, PROKR2, PTCH1, POU1F1), the GH-IGF-1 or IGF-2 axis (GHSR, IGFALS, IGF1R, STAT3, HMGA2), 2/74 (3%) the thyroid axis (TRHR, THRA), 17/74 (23%) the cartilaginous matrix (ACAN, various collagens, FLNB, MATN3), and 7/74 (9%) the paracrine chondrocyte regulation (FGFR3, FGFR2, NPR2). In 12/74 (16%), we revealed P/LP affecting fundamental intracellular/intranuclear processes (CDC42, KMT2D, LMNA, NSD1, PTPN11, SRCAP, SON, SOS1, SOX9, TLK2). SHOX deficiency was found in 7/74 (9%), Silver-Russell syndrome in 12/74 (16%) (11p15, UPD7), and miscellaneous chromosomal aberrations in 5/74 (7%) children. CONCLUSIONS: The high diagnostic yield sheds a new light on the genetic landscape of SGA-SS, with a central role for the growth plate with substantial contributions from the GH-IGF-1 and thyroid axes and intracellular regulation and signalling.

• Klíčová slova
• GH-IGF-1 axis, Genetics, Growth plate, Short stature, Small for gestational age,
• MeSH
• dítě MeSH
• gestační stáří MeSH
• hypotrofický novorozenec MeSH
• insulinu podobný růstový faktor I MeSH
• lidé MeSH
• lidský růstový hormon * genetika   MeSH
• nanismus * MeSH
• novorozenec MeSH
• poruchy růstu genetika   diagnóza   MeSH
• protein SHOX MeSH
• Silverův-Russellův syndrom * genetika   MeSH
• tělesná výška genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• insulinu podobný růstový faktor I MeSH
• lidský růstový hormon * MeSH
• protein SHOX MeSH
• SHOX protein, human MeSH Prohlížeč