Copy number variation analysis in single-suture craniosynostosis: multiple rare variants including RUNX2 duplication in two cousins with metopic craniosynostosis.
Bottom Line: We identified a 1.1 Mb duplication encompassing RUNX2 in two affected cousins with metopic synostosis and hypodontia.Given that RUNX2 is required as a master switch for osteoblast differentiation and interacts with TWIST1, mutations in which also cause craniosynostosis, we conclude that the duplication in this family is pathogenic, albeit with reduced penetrance.In addition, we find that a total of 7.5% of individuals with single-suture synostosis in our series have at least one rare deletion or duplication that contains genes and that has not been previously reported in unaffected individuals.
Affiliation: Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA. email@example.comShow MeSH
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Mentions: We identified one individual with metopic synostosis and a large heterozygous deletion of chromosome 9q22 encompassing 33 genes (patient 4038; Fig. 2A). Since entering the study as an infant, this patient has had severe developmental delay. There are several reports in the literature of similar interstitial deletions of 9q [Boonen et al., 2005; Redon et al., 2006; Nowakowska et al., 2007]. Two patients with large deletions of 9q22 were both described with trigonocephaly [Redon et al., 2006]. The deletion in our patient, which is smaller than the previously reported deletions, supports the hypothesis that there is a gene influencing cranial development and narrows the critical region. Although parental DNA was unavailable for analysis, all cases reported to date are de novo.
Affiliation: Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA. firstname.lastname@example.org