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Isolated sagittal and coronal craniosynostosis associated with TWIST box mutations.
Am J Med Genet A 2007; 143A(7):678-86AJ

Abstract

Craniosynostosis, the premature fusion of one or more cranial sutures, affects 1 in 2,500 live births. Isolated single-suture fusion is most prevalent, with sagittal synostosis occurring in 1/5,000 live births. The etiology of isolated (nonsyndromic) single-suture craniosynostosis is largely unknown. In syndromic craniosynostosis, there is a highly nonrandom pattern of causative autosomal dominant mutations involving TWIST1 and fibroblast growth factor receptors (FGFRs). Prior to our study, there were no published TWIST1 mutations in the anti-osteogenic C-terminus, recently coined the TWIST Box, which binds and inhibits RUNX2 transactivation. RUNX2 is the principal master switch for osteogenesis. We performed mutational analysis on 164 infants with isolated, single-suture craniosynostosis for mutations in TWIST1, the IgIIIa exon of FGFR1, the IgIIIa and IgIIIc exons of FGFR2, and the Pro250Arg site of FGFR3. We identified two patients with novel TWIST Box mutations: one with isolated sagittal synostosis and one with isolated coronal synostosis. Kress et al. [2006] reported a TWIST Box "nondisease-causing polymorphism" in a patient with isolated sagittal synostosis. However, compelling evidence suggests that their and our sequence alterations are pathogenic: (1) a mouse with a mutation of the same residue as our sagittal synostosis patient developed sagittal synostosis, (2) mutation of the same residue precluded TWIST1 interaction with RUNX2, (3) each mutation involved nonconservative amino acid substitutions in highly conserved residues across species, and (4) control chromosomes lacked TWIST Box sequence alterations. We suggest that genetic testing of patients with isolated sagittal or coronal synostosis should include TWIST1 mutational analysis.

Authors+Show Affiliations

Division of Craniofacial Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195-6320, USA. mseto@u.washington.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17343269

Citation

Seto, Marianne L., et al. "Isolated Sagittal and Coronal Craniosynostosis Associated With TWIST Box Mutations." American Journal of Medical Genetics. Part A, vol. 143A, no. 7, 2007, pp. 678-86.
Seto ML, Hing AV, Chang J, et al. Isolated sagittal and coronal craniosynostosis associated with TWIST box mutations. Am J Med Genet A. 2007;143A(7):678-86.
Seto, M. L., Hing, A. V., Chang, J., Hu, M., Kapp-Simon, K. A., Patel, P. K., ... Cunningham, M. L. (2007). Isolated sagittal and coronal craniosynostosis associated with TWIST box mutations. American Journal of Medical Genetics. Part A, 143A(7), pp. 678-86.
Seto ML, et al. Isolated Sagittal and Coronal Craniosynostosis Associated With TWIST Box Mutations. Am J Med Genet A. 2007 Apr 1;143A(7):678-86. PubMed PMID: 17343269.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Isolated sagittal and coronal craniosynostosis associated with TWIST box mutations. AU - Seto,Marianne L, AU - Hing,Anne V, AU - Chang,Jocelyn, AU - Hu,Ming, AU - Kapp-Simon,Kathleen A, AU - Patel,Pravin K, AU - Burton,Barbara K, AU - Kane,Alex A, AU - Smyth,Matthew D, AU - Hopper,Richard, AU - Ellenbogen,Richard G, AU - Stevenson,Kevin, AU - Speltz,Matthew L, AU - Cunningham,Michael L, PY - 2007/3/9/pubmed PY - 2007/10/4/medline PY - 2007/3/9/entrez SP - 678 EP - 86 JF - American journal of medical genetics. Part A JO - Am. J. Med. Genet. A VL - 143A IS - 7 N2 - Craniosynostosis, the premature fusion of one or more cranial sutures, affects 1 in 2,500 live births. Isolated single-suture fusion is most prevalent, with sagittal synostosis occurring in 1/5,000 live births. The etiology of isolated (nonsyndromic) single-suture craniosynostosis is largely unknown. In syndromic craniosynostosis, there is a highly nonrandom pattern of causative autosomal dominant mutations involving TWIST1 and fibroblast growth factor receptors (FGFRs). Prior to our study, there were no published TWIST1 mutations in the anti-osteogenic C-terminus, recently coined the TWIST Box, which binds and inhibits RUNX2 transactivation. RUNX2 is the principal master switch for osteogenesis. We performed mutational analysis on 164 infants with isolated, single-suture craniosynostosis for mutations in TWIST1, the IgIIIa exon of FGFR1, the IgIIIa and IgIIIc exons of FGFR2, and the Pro250Arg site of FGFR3. We identified two patients with novel TWIST Box mutations: one with isolated sagittal synostosis and one with isolated coronal synostosis. Kress et al. [2006] reported a TWIST Box "nondisease-causing polymorphism" in a patient with isolated sagittal synostosis. However, compelling evidence suggests that their and our sequence alterations are pathogenic: (1) a mouse with a mutation of the same residue as our sagittal synostosis patient developed sagittal synostosis, (2) mutation of the same residue precluded TWIST1 interaction with RUNX2, (3) each mutation involved nonconservative amino acid substitutions in highly conserved residues across species, and (4) control chromosomes lacked TWIST Box sequence alterations. We suggest that genetic testing of patients with isolated sagittal or coronal synostosis should include TWIST1 mutational analysis. SN - 1552-4825 UR - https://www.unboundmedicine.com/medline/citation/17343269/Isolated_sagittal_and_coronal_craniosynostosis_associated_with_TWIST_box_mutations_ L2 - https://doi.org/10.1002/ajmg.a.31630 DB - PRIME DP - Unbound Medicine ER -