IGF1R Variants Associated with Isolated Single Suture Craniosynostosis

Overview

Journal Am J Med Genet A

Specialty Genetics

Date 2011 Jan 5

PMID 21204214

Citations 16

Authors

Michael L Cunningham

Jeremy A Horst

Mark J Rieder

Anne V Hing

Ian B Stanaway

Sarah S Park

Ram Samudrala

Matthew L Speltz

Affiliations

Soon will be listed here.

Abstract

The genetic contribution to the pathogenesis of isolated single suture craniosynostosis is poorly understood. The role of mutations in genes known to be associated with syndromic synostosis appears to be limited. We present our findings of a candidate gene resequencing approach to identify rare variants associated with the most common forms of isolated craniosynostosis. Resequencing of the coding regions, splice junction sites, and 5' and 3' untranslated regions of 27 candidate genes in 186 cases of isolated non-syndromic single suture synostosis revealed three novel and two rare sequence variants (R406H, R595H, N857S, P190S, M446V) in insulin-like growth factor I receptor (IGF1R) that are enriched relative to control samples. Mapping the resultant amino acid changes to the modeled homodimer protein structure suggests a structural basis for segregation between these and other disease-associated mutations found in IGF1R. These data suggest that IGF1R mutations may contribute to the risk and in some cases cause single suture craniosynostosis.

Citing Articles

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