A novel RUNX2 missense mutation predicted to disrupt DNA binding causes cleidocranial dysplasia in a large Chinese family with hyperplastic nails

Tang, Shaohua; Xu, Qiyu; Xu, Xueqin; Du, Jicheng; Xue-Mei, Yang; Jiang, Yusheng; Wang, Xiaoqin; Speck, Nancy A.; Huang, Taosheng

doi:10.1186/1471-2350-8-82

Cited by 17 publications

(15 citation statements)

References 29 publications

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“…Majority of RUNX2 mutations in individuals suffering from classic CCD occur in the runt domain and the most common DNA disruptions are missense mutations that prevent RUNX2 binding to DNA or nonsense mutations that result in biosynthesis of truncated protein. While missense mutations are uniquely found within runt‐domain region, nonsense and frame‐shift types were described throughout the gene (Fig. , Table ).…”

Section: Mutations In Human Runx2mentioning

confidence: 99%

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Cleidocranial dysplasia and RUNX2‐clinical phenotype–genotype correlation

et al. 2016

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Runt-related transcription factor 2 (RUNX2/Cbfa1) is the main regulatory gene controlling skeletal development and morphogenesis in vertebrates. It is located on chromosome 6p21 and has two functional isoforms (type I and type II) under control of two alternate promoters (P1 and P2). Mutations within RUNX2 are linked to Cleidocranial dysplasia syndrome (CCD) in humans. CCD is an autosomal skeletal disorder characterized by several features such as delayed closure of fontanels, dental abnormalities and hypoplastic clavicles. Here, we summarize recent knowledge about RUNX2 function, mutations and their phenotypic consequences in patients.

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Section: Mutations In Human Runx2mentioning

confidence: 99%

“…Mutations within the gene or its regulatory regions are commonly found in CCD patients. Further studies are however necessary to establish in more detail the genotype-phenotype correlation ( Table 2) (63,74,86,87,89,90,92) and to fully understand mechanism of underlying pathogenesis of CCD.…”

Section: Genotype-phenotype Correlationmentioning

confidence: 99%

Cleidocranial dysplasia and RUNX2‐clinical phenotype–genotype correlation

et al. 2016

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“…The CCD locus has been mapped to chromosome 6p21, where the gene for the osteoblast‐specific transcription factor runt‐related transcription factor 2 ( RUNX2 ) (also known as CBFA1 , OSF2 , AML3 , and PEBP2A ) is located . So far, more than 90 unique heterozygous mutations in RUNX2 have been reported worldwide in familial and sporadic cases of CCD; however, only a few reports have been published on mutations of RUNX2 in Chinese patients with CCD, and most of these are mutations resulting in premature termination and presumably in defective DNA binding .…”

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Novel RUNX2 frameshift mutations in Chinese patients with cleidocranial dysplasia

Huang

Song

Zhang

et al. 2013

European J Oral Sciences

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Cleidocranial dysplasia (CCD) is a skeletal disorder caused by heterozygous mutations in the runt-related transcription factor 2 (RUNX2) gene. We evaluated the phenotypes of eight Chinese patients with CCD from three unrelated families followed by analysis of the RUNX2 genes. Three different RUNX2 frameshift mutations were identified. Two of the mutations are novel (c.887insC and c.592delA) and one (c.90insC) has been described previously. Surprisingly, the patient with the most severely truncated RUNX2 protein (c.90insC) had the mildest phenotype. The RUNX2 mutations identified were assessed for their effect on the subcellular localization of the mutant RUNX2 proteins because of previously reported inconsistent findings. All three mutant proteins showed at least partially impaired nuclear localization compared with wild-type RUNX2, which was localized exclusively in the nucleus. Our findings support the notion that haploinsufficiency of RUNX2 may be mainly responsible for CCD. However, because the correlation between the severity of the phenotype and the degree of mutational impairment of RUNX2 is not consistent, other factors, such as nonsense-mediated mRNA decay and negative dominant effects, may also play a role. In addition, we show that despite the presence of the best characterized nuclear localization signal, nuclear translocation of truncated RUNX2 can be inhibited, possibly as a result of precipitation in the cytoplasm.

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“…As manifestações clínicas presentes na paciente tais como baixa estatura, pescoço largo, hipertelorismo ocular, braquicefalia com abaulamento frontal e parietal, hipoplasia do terço médio estão de acordo com a literatura pesquisada (SILVA JÚNIOR et al, 2007;TANG et al,2007).…”

Section: Discussionunclassified

Displasia Cleidocraniana

Farias¹

2010

R Bras Ci Saúde

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A novel RUNX2 missense mutation predicted to disrupt DNA binding causes cleidocranial dysplasia in a large Chinese family with hyperplastic nails

Abstract: Background: Cleidocranial dysplasia (CCD) is a dominantly inherited disease characterized by hypoplastic or absent clavicles, large fontanels, dental dysplasia, and delayed skeletal development. The purpose of this study is to investigate the genetic basis of Chinese family with CCD.

Cited by 17 publications

References 29 publications

Cleidocranial dysplasia and RUNX2‐clinical phenotype–genotype correlation

Cleidocranial dysplasia and RUNX2‐clinical phenotype–genotype correlation

Novel RUNX2 frameshift mutations in Chinese patients with cleidocranial dysplasia

Displasia Cleidocraniana

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