A further mutation of the FGFR2 tyrosine kinase domain in mild Crouzon syndrome

Ravel, Thomy de; Taylor, Indira B.; Oostveldt, Alex J T Van; Fryns, Jean‐Pierre; Wilkie, Andrew O.M.

doi:10.1038/sj.ejhg.5201325

Cited by 20 publications

(14 citation statements)

References 14 publications

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“…TWIST1 mutations were some of the first genetic defects linked to craniosynostosis in humans [27–29]. In addition, mutations within FGFR1–3 are known to cause craniosynostosis in humans [1–3, 15].…”

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of Twist1 and FGF Receptors in a Rabbit Model of Craniosynostosis: Likely Exclusion as the Loci of Origin

Gallo

Cray

Durham

et al. 2013

International Journal of Genomics

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Craniosynostosis is the premature fusion of the cranial vault sutures. We have previously described a colony of rabbits with a heritable pattern of nonsyndromic, coronal suture synostosis; however, the underlying genetic defect remains unknown. We now report a molecular analysis to determine if four genes implicated in human craniosynostosis, TWIST1 and fibroblast growth factor receptors 1–3 (FGFR1–3), could be the loci of the causative mutation in this unique rabbit model. Single nucleotide polymorphisms (SNPs) were identified within the Twist1, FGFR1, and FGFR2 genes, and the allelic patterns of these silent mutations were examined in 22 craniosynostotic rabbits. SNP analysis of the Twist1, FGFR1, and FGFR2 genes indicated that none were the locus of origin of the craniosynostotic phenotype. In addition, no structural mutations were identified by direct sequence analysis of Twist1 and FGFR3 cDNAs. These data indicate that the causative locus for heritable craniosynostosis in this rabbit model is not within the Twist1, FGFR1, and FGFR2 genes. Although a locus in intronic or flanking sequences of FGFR3 remains possible, no direct structural mutation was identified for FGFR3.

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Section: Discussionmentioning

confidence: 99%

Molecular Analysis of Twist1 and FGF Receptors in a Rabbit Model of Craniosynostosis: Likely Exclusion as the Loci of Origin

Gallo

Cray

Durham

et al. 2013

International Journal of Genomics

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“…Mutations that strengthen the interactions between the C-helix and the A-loop, are also shown to indirectly weaken this molecular brake and thereby shift equilibrium in favor of the active state. These changes also correlate with known tyrosine kinase-related diseases [14].…”

Section: Introductionmentioning

confidence: 80%

Tyrosine kinase inhibition: Ligand binding and conformational change in c‐Kit and c‐Abl

Healy¹,

Johnson²,

Hauser³

et al. 2009

FEBS Letters

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a b s t r a c tThe conformational flexibility exhibited by protein kinases poses an enormous challenge to the design of cancer therapeutics. Additionally the high degree of structural conservation within the kinase superfamily often leads to inhibitors that exhibit little selectivity and substantial cross reactivity. This work investigates the conformational changes that accompany the binding of Gleevec, or imatinib mesylate, to the tyrosine kinases c-Kit and c-Abl. Our analysis is that this fit is driven, at least in part, by the need to exclude water from solvent-exposed backbone hydrogen bonds. Both experimental and molecular modeling studies of the active state inhibitor of the tyrosine kinase c-Abl indicate that solvent exclusion also plays a role in this system.

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“…Individual variability in alternative splicing of exon 9 in patients carrying the A362S mutation may contribute to the phenotypic spectrum and seeming non‐penetrance of this mutation. Several additional mechanisms may lead to the variability observed in Crouzon families, as mild mutations in FGFR2 have been previously reported in other regions of the protein, including the tyrosine kinase domain 8 …”

Section: Discussionmentioning

confidence: 99%

Bilateral exophthalmos: Report of a case and review of a fibroblast growth factor receptor 2 mutation associated with non‐penetrant Crouzon syndrome

Quintero‐Rivera¹,

Martinez‐Agosto

2010

J Paediatrics Child Health

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The differential diagnosis of exophthalmos requires careful examination to identify potentially serious aetiologies. We present the case of a child with exophthalmos in whom genetic analysis identified a mutation in the fibroblast growth factor receptor 2 associated with Crouzon syndrome. The variable presentation should remind paediatricians to consider mutations in fibroblast growth factor receptor 2 among the aetiologies of exophthalmos.

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A further mutation of the FGFR2 tyrosine kinase domain in mild Crouzon syndrome

Cited by 20 publications

References 14 publications

Molecular Analysis of Twist1 and FGF Receptors in a Rabbit Model of Craniosynostosis: Likely Exclusion as the Loci of Origin

Molecular Analysis of Twist1 and FGF Receptors in a Rabbit Model of Craniosynostosis: Likely Exclusion as the Loci of Origin

Tyrosine kinase inhibition: Ligand binding and conformational change in c‐Kit and c‐Abl

Bilateral exophthalmos: Report of a case and review of a fibroblast growth factor receptor 2 mutation associated with non‐penetrant Crouzon syndrome

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