RUNX2 mutations in Taiwanese patients with cleidocranial dysplasia.
ABSTRACT Cleidocranial dysplasia (CCD) is an autosomal dominant human skeletal disorder comprising hypoplastic clavicles, wide cranial sutures, supernumerary teeth, short stature, and other skeletal abnormalities. It is known that mutations in the human RUNX2 gene mapped at 6p21 are responsible for CCD. We analyzed the mutation patterns of the RUNX2 gene by direct sequencing in six Taiwanese index cases with typical CCD. One of the patients was a familial case and the others were sporadic cases. Sequencing identified four mutations. Three were caused by single nucleotide substitutions, which created a nonsense (p.R391X), two were missense mutations (p.R190W, p.R225Q), and the forth was a novel mutation (c.1119delC), a one-base deletion. Real time quantitative PCR adapted to determine copy numbers of the promoter, all exons and the 3'UTR region of the RUNX2 gene detected the deletion of a single allele in a sporadic case. The results extend the spectrum of RUNX2 mutations in CCD patients and indicate that complete deletions of the RUNX2 gene should be considered in those CCD patients lacking a point mutation detected by direct sequencing.
Full-textDOI: · Available from: Wei-De Lin, Jan 06, 2015
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ABSTRACT: Cleidocranial dysplasia is a rare hereditary skeletal disorder due to heterozygous loss of function mutations in the RUNX2 gene that encodes runt-related transcription factor 2 (RUNX2). Here we report a 52 year-old woman with cleidocranial dysplasia due to a novel RUNX2 mutation. A 52 year-old Han Chinese woman presented with short stature and skeletal dysplasia that was first noted during early childhood. She was 153 cm in height and 40 kg in weight. Her skull was deformed with hypertelorism, midface hypoplasia, protrusion of chin, and dental abnormalities. Radiological examination revealed shortened clavicles and depressed skull bone and that were consistent with the clinical diagnosis of cleidocranial dysplasia. There was no family history of a similar skeletal disorder. We sequenced the RUNX2 gene and discovered a novel heterozygous mutation in exon 3 (c.476 del G, p.G159fs175X) that is predicted to cause a frameshift and premature termination that leads to the loss of the final 347 amino acid residues. This severely truncated protein is expected to be inactive. RUNX2 gene controls osteoblast differentiation and chondrocyte maturation. Around 90 RUNX2 mutations have been discovered in patients with cleidocranial dysplasia. We identified a case of cleidocranial dysplasia due to a novel mutation of RUNX2 gene at exon 3 (c.476 del G).
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ABSTRACT: The early identification of hereditary syndromes is essential for planning interventions to reduce the risk of complications. Unfortunately, clinical phenotypes in the first years of life and in mild cases are often poorly characterized. Moreover, some disease symptoms are common for several genetic conditions. In this report, a child was initially misdiagnosed with hypermobile Ehlers-Danlos syndrome (EDS); the correct diagnosis of cleidocranial dysplasia (CCD), which was confirmed by genetic findings, was not made until several years later. This case teaches that diagnoses of hereditary syndromes must be performed carefully and take clinical history, symptoms, and genetic analyses into account.Italian Journal of Pediatrics 05/2014; 40(1):49. DOI:10.1186/1824-7288-40-49