<abstract xmlns="http://www.w3.org/1999/xhtml">Molecular genetic testing in craniosynostosis leads to the detection of the mutations in the genes encoding fibroblast growth factor receptors (FGFR), providing information about the etiology of the genetic disorder. Muenke syndrome is produced by p.Pro250Arg mutation in FGFR3 gene with evidence of variable expressivity, representing 8% of the syndromic craniosynostoses.Here, we present the identification of a p.Pro250Arg pathogenic mutation (c.749C>G) in the FGFR3 gene using Multiplex Ligation-dependent Probes Amplification (MLPA) analysis in conjunction with Sanger sequencing in a patient with craniosynostosis and mild intellectual disability. The MLPA analysis detected a reduced signal of the probe, at the site of the c.749C>G mutation, defined by the presence of one allele of C749>G mutation in the FGFR3 gene, exon 7. Sanger sequencing was performed for confirmation and identified heterozygous p.Pro250Arg pathogenic variant (c.749C>G) in exon 7 of the FGFR3.In conclusion, we assessed the validity and clinical utility of the combined molecular genetic techniques, MLPA analysis, and Sanger sequencing, for craniosynostosis and intellectual disability, improving not only the diagnostic testing but also the genetic counseling and management of the disorder.</abstract>

Molecular genetic testing in craniosynostosis leads to the detection of the mutations in the genes encoding fibroblast growth factor receptors (FGFR), providing information about the etiology of the genetic disorder. Muenke syndrome is produced by p.Pro250Arg mutation in FGFR3 gene with evidence of variable expressivity, representing 8% of the syndromic craniosynostoses.Here, we present the identification of a p.Pro250Arg pathogenic mutation (c.749C>G) in the FGFR3 gene using Multiplex Ligation-dependent Probes Amplification (MLPA) analysis in conjunction with Sanger sequencing in a patient with craniosynostosis and mild intellectual disability. The MLPA analysis detected a reduced signal of the probe, at the site of the c.749C>G mutation, defined by the presence of one allele of C749>G mutation in the FGFR3 gene, exon 7. Sanger sequencing was performed for confirmation and identified heterozygous p.Pro250Arg pathogenic variant (c.749C>G) in exon 7 of the FGFR3.In conclusion, we assessed the validity and clinical utility of the combined molecular genetic techniques, MLPA analysis, and Sanger sequencing, for craniosynostosis and intellectual disability, improving not only the diagnostic testing but also the genetic counseling and management of the disorder.

The utility of molecular genetic techniques in craniosynostosis cases associated with intellectual disability

Emergency Clinical County Hospital Târgu Mureș

University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureş

Revista Romana de Medicina de Laborator

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Molecular genetic testing in craniosynostosis leads to the detection of the mutations in the genes encoding fibroblast growth factor receptors (FGFR),...

The utility of molecular genetic techniques in craniosynostosis cases associated with intellectual disability

Publicado en línea: 29 oct 2018

Páginas: 471 - 477

Recibido: 29 jul 2018

Aceptado: 18 sept 2018

DOI: https://doi.org/10.2478/rrlm-2018-0033

Palabras clave
craniosynostosis, FGFR3, Pro250Arg mutation, MLPA analysis, Sanger sequencing

© 2018 Alina Bogliş et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

The utility of molecular genetic techniques in craniosynostosis cases associated with intellectual disability

Publicado en línea: 29 oct 2018

Páginas: 471 - 477

Recibido: 29 jul 2018

Aceptado: 18 sept 2018

DOI: https://doi.org/10.2478/rrlm-2018-0033

Palabras clavecraniosynostosis, FGFR3, Pro250Arg mutation, MLPA analysis, Sanger sequencing

© 2018 Alina Bogliş et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Palabras clave
craniosynostosis, FGFR3, Pro250Arg mutation, MLPA analysis, Sanger sequencing