RUNX2 quadruplication: additional evidence toward a new form of syndromic craniosynostosis.
The RUNX2 transcription factor regulates osteoblast differentiation. Its absence, as with cleidocranial dysplasia, results in deficient bone formation. However, its excess seems to follow a dose response of over ossification. RUNX2 duplications (3 copies) are exceedingly rare but have been reported to cause craniosynostosis. There are no existing reports of quadruplications (4 copies). We present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. Further characterization of this osteogenic pathway may aid in our understanding of the pathogenesis and subsequent prevention and treatment of syndromic craniosynostosis.
Department of Surgery, and †Genetics; ‡Pediatrics, Comer Children's Hospital, University of Chicago Medical Center, Chicago, IL 60637, USA.
Matthew R
MR
Greives
Eric A
EA
Odessey
Darrel J
DJ
Waggoner
Deana S
DS
Shenaq
Swaroop
S
Aradhya
Allison
A
Mitchell
Emma
E
Whitcomb
Neil
N
Warshawsky
Tong-Chuan
TC
He
Russell R
RR
Reid
D000015:Abnormalities, Multiple; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D003398:Craniosynostoses / Q000235:genetics* / Q000601:surgery; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D046228:Microarray Analysis; D017422:Sequence Analysis, DNA
D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human