scholarly journals Novel mutation detection of fibroblast growth factor receptor 1 (FGFR1) gene, FGFR2IIIa, FGFR2IIIb, FGFR2IIIc, FGFR3, FGFR4 gene for craniosynostosis: A prospective study in Asian Indian patient

2015 ◽  
Vol 10 (3) ◽  
pp. 207 ◽  
Author(s):  
Mayadhar Barik ◽  
Minu Bajpai ◽  
Arun Malhotra ◽  
JyotishChandra Samantaray ◽  
Sadananda Dwivedi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Asian Indian ◽  
Mutation Detection ◽  
Fibroblast Growth Factor Receptor ◽  
Novel Mutation ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Indian Patient ◽  
Fgfr1 Gene ◽  
A Prospective Study

scholarly journals A Mutation in the Fibroblast Growth Factor Receptor 1 Gene Causes Fully Penetrant Normosmic Isolated Hypogonadotropic Hypogonadism

2007 ◽  
Vol 92 (3) ◽  
pp. 1155-1158 ◽  
Author(s):  
Ning Xu ◽  
Yu Qin ◽  
Richard H. Reindollar ◽  
Sandra P. T. Tho ◽  
Paul G. McDonough ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Molecular Analysis ◽  
Autosomal Dominant ◽  
Fibroblast Growth Factor Receptor ◽  
Hypogonadotropic Hypogonadism ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Associated Anomalies ◽  
Fgfr1 Gene

Abstract Context: Kallmann syndrome (KS) consists of idiopathic hypogonadotropic hypogonadism (IHH) and anosmia/hyposmia. Currently, the fibroblast growth factor receptor 1 (FGFR1) gene is the only known autosomal dominant cause of KS, which is also associated with synkinesia, midfacial defects, and dental agenesis. Objective: Mutations in FGFR1 typically demonstrate reduced penetrance, variable expressivity, and until recently have been exclusively identified in families with anosmia. The purpose of this study was to determine whether FGFR1 mutations were present in a unique family with autosomal dominant, fully penetrant, normosmic IHH. Design: The study is a review of detailed clinical findings, dynamic endocrine studies, and performance of a molecular analysis of the FGFR1 gene. Setting: The study was carried out in an academic medical center. Patients: All four affected individuals have complete IHH with full penetrance but no anosmia/hyposmia, and they have none of the FGFR1-associated anomalies. In addition, no other family member has anosmia. Inverventions: Interventions included detailed phenotype characterization including history, physical exam, smell testing, dynamic pituitary testing, brain imaging, and molecular analysis. Main Outcome Measures: Outcome was measured by the determination of the severity of IHH, olfactory function, and sequence of the FGFR1 gene. Results: The same heterozygous nonsense mutation, Arg622X, was present in all four affected members, but not in three unaffected members or 100 controls. The mutation is predicted to encode a truncated protein or result in nonsense-mediated decay. Conclusions: Our findings indicate that mutations in the FGFR1 gene can cause normosmic, fully penetrant, complete IHH with little or no variable expressivity, and without the other FGFR1-associated anomalies typically found in KS.

scholarly journals Bimodal, Reciprocal Regulation of Fibroblast Growth Factor Receptor 1 Promoter Activity by BTEB1/KLF9 during Myogenesis

2010 ◽  
Vol 21 (15) ◽  
pp. 2780-2787 ◽  
Author(s):  
Darrion L. Mitchell ◽  
Joseph X. DiMario
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Binding Site ◽  
Fibroblast Growth Factor ◽  
Promoter Activity ◽  
Fibroblast Growth Factor Receptor ◽  
Myogenic Differentiation ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Fgfr1 Gene

Expression of the gene encoding fibroblast growth factor receptor 1 (FGFR1) and subsequent FGFR1-mediated cell signaling controls numerous developmental and disease-related processes. The transcriptional regulation of the FGFR1 gene is central to these developmental events and serves as a molecular model for understanding transcriptional control of growth factor receptor genes. The FGFR1 promoter is activated in proliferating myoblasts via several Sp1-like binding elements. These elements display varying levels of activation potential, suggesting that unique protein-DNA complexes coordinate FGFR1 gene expression via each of these sites. The Krüppel-like factor, BTEB1/KLF9, was expressed in both proliferating myoblasts and differentiated myotubes in vitro. The BTEB1 protein was nuclear-localized in both cell types. BTEB1 activated the FGFR1 promoter via interaction with the Sp1-like binding site located at −59 bp within the FGFR1 promoter. FGFR1 gene expression is down-regulated during myogenic differentiation, and FGFR1 promoter activity is correspondingly reduced. This reduction in FGFR1 promoter activity was attributable to BTEB1 interaction with the same Sp1-like binding site located at −59 bp in the FGFR1 promoter. Therefore, BTEB1 is capable of functioning as a transcriptional activator and repressor of the same promoter via the same DNA-binding element and demonstrates a novel, bimodal role of BTEB1 during myogenesis.

scholarly journals Novel Mutations in FGFR1 Causing Idiopathic Hypogonadotropic Hypogonadism: A Cohort Study in Eastern Indian Population

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A507-A508
Author(s):  
Arjun Baidya ◽  
Saptarshi Datta ◽  
Satinath Mukhopadhyay ◽  
Sib Shankar Roy
Keyword(s):  
Growth Factor ◽  
Olfactory Bulb ◽  
Fibroblast Growth Factor ◽  
Indian Population ◽  
Fibroblast Growth Factor Receptor ◽  
Hypogonadotropic Hypogonadism ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Sporadic Cases ◽  
Fgfr1 Gene

Abstract Introduction: IHH is a clinically and genetically heterogeneous condition with more than 80 different mutations described in literature, some of the important being KAL-1 (anosmin), fibroblast growth factor receptor-1 (FGFR1) and fibroblast growth factor-8 (FGF8). Objective: To characterize the clinical findings and molecular analysis of FGFR1 (KAL2) genes in 10 unrelated patients of idiopathic hypogonadotropic hypogonadism with and without hyposmia/anosmia. Methods: After confirming the diagnosis of IHH from detailed history, clinical and biochemical examination the patients were subjected to MRI of pituitary hypothalamic area and olfactory bulb and tract. For genetic analysis PCR of 18 exons was performed on the genomic DNA. The PCR products were purified, sequenced and analysed using BLAST search from NCBI GenBank. Results: We diagnosed ten unrelated sporadic cases of IHH (9 male and 1 female). Out of 10 cases 6 (60%) had anosmia (KS) 4 had normosmia. A variable degree of pubertal development was observed, including various clinical abnormalities, such as micropenis, dental agenesis, skeletal deformity, seizure disorder and bimanual synkinesis. All the patients who had anosmia (KS) had either hypoplasia or aplasia of olfactory bulb and tract on MRI. Two KS patients had novel sporadic FGFR1 mutation, one had a mutation n.2370 C>A detected at exon 10 of FGFR1 gene and another had a mutation n.1875 GA>CA at exon 8C of FGFR1 gene. Discussion: Loss-of-function sequence variants in FGFR1, encoding the fibroblast growth factor receptor-1, account for one autosomal dominant form of KS. Pathogenic changes in KAL1 or FGFR1 have been detected in approximately 20% of the KS patients, which indicates that other responsible genes are still to be discovered. FGFR1 comprises an extracellular region consisting of three immunoglobulin-like domains (D1-D3), a single transmembrane helix, and an intracellular region containing the tyrosine kinase domain. D2, D3 and the short linker between them house all the determinants of ligand (FGF) binding and specificity. In addition, alternative splicing of exon 8, encoding the D3 C-terminal half, leads to two FGFR1 isoforms, FGFR1b (exon 8A) and FGFR1c (exon 8B), with different specificities towards FGF ligands. All the pathogenic changes in FGFR1 that have been reported in KS so far disrupt both isoforms of FGFR1 i.e. FGF1b and FGF1c, therefore leaving open the question of which isoform(s) is (are) required in the olfactory bulb morphogenetic process. We identified a new mutation in exon 8C (patient no 2). Conclusions: IHH and KS patients present with broad spectrum of clinical manifestations. We identified two novel mutations in FGFR1 gene in two unrelated sporadic cases of KS in the Indian population.

Study on the polymorphism of fibroblast growth facorreceptor (FGFR1) in sheep

2016 ◽  
Author(s):  
Jun Yan Bai ◽  
Xiao Ping Jia ◽  
You Bing Yang ◽  
You. Zhi Pang ◽  
Yu Qin Wang
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Phylogenetic Species ◽  
Sequencing Technology ◽  
Pcr Product ◽  
Close Relationship ◽  
Fgfr1 Gene ◽  
Tibetan Antelope

The polymorphisms of fibroblast growth factor receptor (FGFR1) were detected in large-tailed Han sheep, small-tailed Han sheep, Yuxi fat-tailed sheep and Lanzhou large-tailed sheep by PCR product sequencing technology. The results showed that FGFR1 gene had 4 mutation sites in large-tailed Han sheep, small-tailed Han sheep, Yuxi fat-tailed sheep and Lanzhou large-tailed sheep, including T558C, G342A, G417A and G420A. FGFR1 gene sequences of different species clustering showed that sheep, buffalo and Tibetan antelope clustered together firstly, suggesting that the three phylogenetic species had a close relationship.

scholarly journals Reversible Kallmann Syndrome, Delayed Puberty, and Isolated Anosmia Occurring in a Single Family with a Mutation in the Fibroblast Growth Factor Receptor 1 Gene

2005 ◽  
Vol 90 (3) ◽  
pp. 1317-1322 ◽  
Author(s):  
Nelly Pitteloud ◽  
James S. Acierno ◽  
Astrid U. Meysing ◽  
Andrew A. Dwyer ◽  
Frances J. Hayes ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Hypogonadotropic Hypogonadism ◽  
Growth Factor Receptor ◽  
Delayed Puberty ◽  
Fibroblast Growth ◽  
Single Family ◽  
Loss Of Function ◽  
Fgfr1 Gene

Kallmann syndrome (KS) is a clinically and genetically heterogeneous disorder. Recently, loss-of-function mutations in the fibroblast growth factor receptor 1 (FGFR1) gene have been shown to cause autosomal dominant KS. To date, the detailed reproductive phenotype of KS associated with mutations in the FGFR1 has yet to be described. We report a kindred comprising a male proband with KS and spontaneous reversibility, whose mother had delayed puberty and whose maternal grandfather isolated anosmia. The proband presented at age 18 yr with KS and was subsequently treated with testosterone (T) therapy. Upon discontinuation of T therapy, he recovered from his hypogonadotropic hypogonadism, as evidenced by a normal LH secretion pattern, sustained normal serum T levels, and active spermatogenesis. The three members of this single family harbor the same FGFR1 mutation (Arg622X) in the tyrosine kinase domain. This report demonstrates 1) the first genetic cause of the rare variant of reversible KS, 2) the reversal of hypogonadotropic hypogonadism in a proband carrying an FGFR1 mutation suggests a role of FGFR1 beyond embryonic GnRH neuron migration, and 3) a loss of function mutation in the FGFR1 gene causing delayed puberty.

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