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Clinical dividends from the molecular genetic diagnosis of craniosynostosis †
Author(s) -
Wilkie Andrew O.M.,
Bochukova Elena G.,
Hansen Ruth M. S.,
Taylor Indira B.,
RannanEliya Sahan V.,
Byren Jo C.,
Wall Steven A.,
Ramos Lina,
Venâncio Margarida,
Hurst Jane A.,
O'Rourke Anthony W.,
Williams Louise J.,
Seller Anneke,
Lester Tracy
Publication year - 2007
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.31905
Subject(s) - craniosynostosis , penetrance , craniosynostoses , mutation , genetics , genetic counseling , genetic heterogeneity , prenatal diagnosis , gene duplication , bioinformatics , biology , phenotype , gene , medicine , pregnancy , fetus
A dozen years have passed since the first genetic lesion was identified in a family with craniosynostosis, the premature fusion of the cranial sutures. Subsequently, mutations in the FGFR2 , FGFR3 , TWIST1 , and EFNB1 genes have been shown to account for ∼25% of craniosynostosis, whilst several additional genes make minor contributions. Using specific examples, we show how these discoveries have enabled refinement of information on diagnosis, recurrence risk, prognosis for mental development, and surgical planning. However, phenotypic variability can present a significant challenge to the clinical interpretation of molecular genetic tests. In particular, the difficulty of analyzing the complex interaction of genetic background and prenatal environment in determining clinical features, limits the value of identifying low penetrance mutations. © 2007 Wiley‐Liss, Inc.