Clinical management and emerging therapies of FGFR3-related skeletal dysplasia in childhood

Kim, Hwa Young; Ko, Jung Min

doi:10.6065/apem.2244114.057

Cited by 9 publications

(14 citation statements)

References 56 publications

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“…A large number of DEGs that play essential roles in the regulation of bone development were identified. Key candidate genes were further identified through a combination of functional analysis with literature mining, including NKX3.2 [ 34 , 35 , 36 , 37 , 38 , 39 , 40 ], WLS [ 41 , 42 , 43 ], GREM1 [ 44 , 45 , 46 ], FGFR3 [ 47 , 48 , 49 , 50 , 51 ], HHEX [ 52 , 53 , 54 ], COL11A1 [ 55 , 56 , 57 ], and WNT16 [ 58 , 59 ]. These genes were mainly enriched in the BMP, FGF, Wnt, and Notch signaling pathways, suggesting that they are involved in the development of the pig vertebral column.…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of Transcriptome Expression Profiles Reveals miRNA-326–NKX3.2-Regulated Porcine Chondrocyte Differentiation

Luo

Chao

et al. 2023

IJMS

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The porcine body length trait is an essential factor affecting meat production and reproductive performance. It is evident that the development/lengthening of individual vertebrae is one of the main reasons for increases in body length; however, the underlying molecular mechanism remains unclear. In this study, RNA-seq analysis was used to profile the transcriptome (lncRNA, mRNA, and miRNA) of the thoracic intervertebral cartilage (TIC) at two time points (1 and 4 months) during vertebral column development in Yorkshire (Y) and Wuzhishan pigs (W). There were four groups: 1- (Y1) and 4-month-old (Y4) Yorkshire pigs and 1- (W1) and 4-month-old (W4) Wuzhishan pigs. In total, 161, 275, 86, and 126 differentially expressed (DE) lncRNAs, 1478, 2643, 404, and 750 DE genes (DEGs), and 74,51, 34, and 23 DE miRNAs (DE miRNAs) were identified in the Y4 vs. Y1, W4 vs. W1, Y4 vs. W4, and Y1 vs. W1 comparisons, respectively. Functional analysis of these DE transcripts (DETs) demonstrated that they had participated in various biological processes, such as cellular component organization or biogenesis, the developmental process, the metabolic process, bone development, and cartilage development. The crucial bone development-related candidate genes NK3 Homeobox 2 (NKX3.2), Wnt ligand secretion mediator (WLS), gremlin 1 (GREM1), fibroblast growth factor receptor 3 (FGFR3), hematopoietically expressed homeobox (HHEX), (collagen type XI alpha 1 chain (COL11A1), and Wnt Family Member 16 (WNT16)) were further identified by functional analysis. Moreover, lncRNA, miRNA, and gene interaction networks were constructed; a total of 55 lncRNAs, 6 miRNAs, and 7 genes formed lncRNA–gene, miRNA–gene, and lncRNA–miRNA–gene pairs, respectively. The aim was to demonstrate that coding and non-coding genes may co-regulate porcine spine development through interaction networks. NKX3.2 was identified as being specifically expressed in cartilage tissues, and it delayed chondrocyte differentiation. miRNA-326 regulated chondrocyte differentiation by targeting NKX3.2. The present study provides the first non-coding RNA and gene expression profiles in the porcine TIC, constructs the lncRNA–miRNA–gene interaction networks, and confirms the function of NKX3.2 in vertebral column development. These findings contribute to the understanding of the potential molecular mechanisms regulating pig vertebral column development. They expand our knowledge about the differences in body length between different pig species and provide a foundation for future studies.

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Section: Discussionmentioning

confidence: 99%

Integrated Analysis of Transcriptome Expression Profiles Reveals miRNA-326–NKX3.2-Regulated Porcine Chondrocyte Differentiation

Luo

Chao

et al. 2023

IJMS

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“…Individuals with monoallelic mutation of NPPC were reported with short stature with a tendency towards the development of small hands [25]. CNP analogues are the first approved precision medicine to enhance bone growth in achondroplasia caused by gain-of-function mutations in FGFR3 [14]. FGF signaling acts through FGFR3 which negatively regulates growth plate chondrogenesis [14].…”

Section: Paracrine Disordermentioning

confidence: 99%

“…CNP analogues are the first approved precision medicine to enhance bone growth in achondroplasia caused by gain-of-function mutations in FGFR3 [14]. FGF signaling acts through FGFR3 which negatively regulates growth plate chondrogenesis [14]. The clinical phenotypes of gain-of-function mutations in FGFR3 include thanatophoric dysplasia, achondroplasia, and hypochondroplasia [14].…”

Section: Paracrine Disordermentioning

confidence: 99%

“…FGF signaling acts through FGFR3 which negatively regulates growth plate chondrogenesis [14]. The clinical phenotypes of gain-of-function mutations in FGFR3 include thanatophoric dysplasia, achondroplasia, and hypochondroplasia [14].…”

Section: Paracrine Disordermentioning

confidence: 99%

“…Recently, several genes involved in the endochondral ossification process and their frequency in ISS conditions have been identified. Furthermore, several reports have demonstrated that mutations in the same genes, such as SHOX, natriuretic peptide receptor B (NPR2), aggrecan (ACAN), and fibroblast growth factor receptor 3 (FGFR3) can cause a wide spectrum of phenotypic abnormalities, ranging from skeletal dysplasia to ISS [13,14]. This review describes the genetic causes of primary growth plate dysfunction that leads to short stature in children.…”

Section: Introductionmentioning

confidence: 99%

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A new era of genetic diagnosis for short stature children: A review

Kim

2022

Precis Future Med

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Children with short stature are often presented to pediatric endocrinologists. Short stature is defined as the height that is more than two standard deviations below the corresponding mean height for a specific age and sex in a reference population. Endocrine dysfunctions, including growth hormone deficiency/insensitivity, hypothyroidism, cortisol excess, precocious puberty, chronic disease (renal disease, diabetes mellitus, or inflammatory disease), and genetic disorders, should be assessed in patients presenting with short stature. In addition to medical history, physical examination, endocrine study, skeletal survey, and genetic testing are important for identifying the cause of short stature. Based on the next-generation sequencing analysis in patients with short stature, different genes that are unrelated to syndromic or non-syndromic short stature were identified. In particular, the genetic causes of short stature disrupting the growth plates and the pituitary-insulin-like growth factor axis have expanded. In recent years, the molecular level of chondrogenesis in the growth plates, including paracrine signals, extracellular matrix, and fundamental intracellular signals, has been reported. Moreover, new insights into the molecular pathogenesis of short stature are emerging. This article aimed to review the genetic causes of primary growth impairment in idiopathic short stature conditions.

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