title: RUNX2 mutations in Chinese patients with cleidocranial dysplasia.
abstract: Cleidocranial dysplasia (CCD) is an autosomal dominant bone disease in humans caused by haploinsufficiency of the RUNX2 gene. The RUNX2 has two major isoforms derived from P1 and P2 promoters. Over 90 mutations of RUNX2 have been reported associated with CCD. In our study, DNA samples of nine individuals from three unrelated CCD families were collected and screened for all exons of RUNX2 and 2 kb of P1 and P2 promoters. We identified two point mutations in the RUNX2 gene in Case 1, including a nonsense mutation (c.577C>T) that has been reported previously and a silent substitution (c.240G>A). In vitro studies demonstrated that c.577C>T mutation led to truncated RUNX2 protein production and diminished stimulating effects on mouse osteocalcin promoter activity when compared with full-length Runx2-II and Runx2-I isoforms. These results confirm that loss of function RUNX2 mutation (c.577C>T) in Case 1 family is responsible for its CCD phenotype.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Pan
authors.forename: Wanfeng
authors.initials: W
authors.lastname: Xu
authors.forename: Nan
authors.initials: N
authors.lastname: He
authors.forename: Xuewu
authors.initials: X
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Darryl Quarles
authors.forename: Honghao
authors.initials: H
authors.lastname: Zhou
authors.forename: Zhousheng
authors.initials: Z
authors.lastname: Xiao
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002681:China; D002973:Cleidocranial Dysplasia / Q000000981:diagnostic imaging / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D011859:Radiography
chemical_list: D018389:Codon, Nonsense; D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human