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IGF1R variants associated with isolated single suture craniosynostosis
Author(s) -
Cunningham Michael L.,
Horst Jeremy A.,
Rieder Mark J.,
Hing Anne V.,
Stanaway Ian B.,
Park Sarah S.,
Samudrala Ram,
Speltz Matthew L.
Publication year - 2011
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.33781
Subject(s) - craniosynostosis , genetics , synostosis , biology , gene , coding region , candidate gene , fibrous joint , anatomy
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. © 2010 Wiley‐Liss, Inc.