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KMID : 0381120220440060683
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Genes and Genomics
2022 Volume.44 No. 6 p.683 ~ p.690
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Identification a novel de novo RUNX2 frameshift mutation associated with cleidocranial dysplasia
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Gong Lei
Odilov Bekzod
Han Feng
Liu Fuqiang
Sun Yujing
Zhang Ningxin
Zuo Xiaolin
Yang Jiaojiao
Wang Shouyu
Hou Xinguo
Ren Jianmin
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Abstract
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Background: Cleidocranial dysplasia (CCD) is a rare genetic disorder affecting bone and cartilage development. Clinical features of CCD comprise short stature, delayed ossification of craniofacial structures with numerous Wormian bones, underdeveloped or aplastic clavicles and multiple dental anomalies. Several studies have revealed that CCD development is strongly linked with different mutations in runt-related transcription factor 2 (RUNX2) gene.
Objective: Identification and functional characterization of RUNX2 mutation associated with CCD.
Methods: We performed genetic testing of a patient with CCD using whole exome sequencing and found a novel RUNX2 frameshift mutation: c.1550delT in a sporadic case. We also compared the functional activity of the mutant and wild-type RUNX2 through immunofluorescence microscopy and osteocalcin promoter luciferase assay.
Results: We found a novel RUNX2 frameshift mutation, c.1550delT (p.Trp518Glyfs*60). Both mutant RUNX2 and wild-type RUNX2 protein were similarly confined in the nuclei. The novel mutation caused abrogative transactivation activity of RUNX2 on osteocalcin promoter.
Conclusions: We explored a novel RUNX2 deletion/frameshift mutation in a sporadic CCD patient. This finding suggests that the VWRPY domain may play a key role in RUNX2 transactivation ability.
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KEYWORD
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RUNX2, Novel mutation, Cleidocranial dysplasia, Genetic disorder
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