Document Detail


Integrated strategy for fast and automated molecular characterization of genes involved in craniosynostosis.
MedLine Citation:
PMID:  17693524     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Craniosynostosis, the premature fusion of 1 or more sutures of the skull, is a common congenital defect, with a prevalence of 1 in 2500 live births. Untreated progressive craniosynostosis leads to inhibition of brain growth and increased intracranial and intraorbital pressure. The heterogeneity of clinical phenotypes and the overlap of the various associated syndromes render the correct diagnosis of the different craniosynostoses particularly difficult. METHODS: To identify 10 common mutations in the genes for fibroblast growth factor receptors 2 and 3 (FGFR2 and FGFR3), we developed a microelectronic microchip assay that exploited the PCR multiplexing format and coupled it with serial addressing and probe hybridization on the same pad. For the molecular characterization of patients who tested negative in the microchip screening, we also developed conditions for denaturing HPLC (DHPLC) analysis of the most mutated regions of FGFR2 and FGFR3 and the entire coding region of the TWIST1 gene. RESULTS: In our cohort of 159 patients with various craniosynostosis syndromes, mutations were found in 100% of patients with Apert syndrome, 83.3% with Pfeiffer syndrome, 72.7% with Crouzon syndrome, 50.0% with Saethre-Chotzen syndrome, 27.7% with plagiocephaly, 31.8% with brachicephaly, 20% of complex cases, and 6.9% of mixed cases. No mutations were found in syndromic cases. CONCLUSIONS: The combined microchip-DHPLC strategy allows rapid and specific molecular diagnosis of craniosynostosis and is an effective tool for the medical and surgical management of these common congenital anomalies in a newborn or an infant with a developmental defect of the cranial vault.
Authors:
Stefania Stenirri; Gabriella Restagno; Giovanni Battista Ferrero; Georgia Alaimo; Luca Sbaiz; Caterina Mari; Lorenzo Genitori; Ferrari Maurizio; Laura Cremonesi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-08-10
Journal Detail:
Title:  Clinical chemistry     Volume:  53     ISSN:  0009-9147     ISO Abbreviation:  Clin. Chem.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-21     Completed Date:  2007-10-25     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9421549     Medline TA:  Clin Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1767-74     Citation Subset:  IM    
Affiliation:
Genomic Unit for the Diagnosis of Human Pathologies, San Raffaele Scientific Institute, Milan, Italy.
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MeSH Terms
Descriptor/Qualifier:
Autoanalysis
Child
Child, Preschool
Chromatography, High Pressure Liquid
Craniosynostoses / diagnosis*,  genetics
Electronics
Humans
Infant
Molecular Diagnostic Techniques
Mutation
Oligonucleotide Array Sequence Analysis
Polymerase Chain Reaction
Receptor, Fibroblast Growth Factor, Type 2 / genetics*
Receptor, Fibroblast Growth Factor, Type 3 / genetics*
Chemical
Reg. No./Substance:
EC 2.7.1.112/FGFR2 protein, human; EC 2.7.1.112/FGFR3 protein, human; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 2; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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