Abstract
Cleidocranial dysplasia (CCD; OMIM: 119600) is a rare autosomal dominant skeletal dysplasia caused by RUNX2 gene mutations. The present study described a sporadic case with CCD. The clinical data of the proband with CCD was reported and genetic analysis was performed. The proband presented with typical CCD features including supernumerary impacted teeth, bilateral clavicle dysplasia, delayed closure of cranial sutures, and short stature; while his hands were normal. Sequencing analysis of the entire coding region of the RUNX2 gene revealed no pathogenic changes; however, copy-number analysis with the Affymetrix HD array found \(\sim \)500 kb genomic microdeletion. Real-time quantitative PCR validated this microdeletion in the 1–4 exons of the RUNX2 gene. The junction point of the breaking DNA was located in the directly oriented AluSz6 and AluSx repetitive elements, indicating that this microdeletion might be generated through an Alu–Alu mediated mechanism. In addition, this microdeletion existed in 21.8% of the asymptomatic mother’s peripheral blood cells, demonstrating that the mosaicism was not associated with CCD phenotypes. In summary, a pathogenic microdeletion in the RUNX2 gene located on chromosome 6 was responsible for CCD.
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Acknowledgements
This work was supported by National Natural Science Foundation of China (81570960), Ministry of Science and Technology of China (2013CB945400), Suzhou Health and Family Planning Commission (SYSD2015093), Advance Research Programme of the Second Affiliated Hospital of Soochow University (SDFEYBS1603), and the Preponderant Clinic Discipline Group Project Funding of the Second Affiliated Hospital of Soochow University (XKQ2015010). We thank Dr Xiao-zhi Wang from Gminix (Shanghai, China) for assistance with bioinformatic analyses.
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Qian, Y., Zhang, Y., Wei, B. et al. A novel Alu-mediated microdeletion in the RUNX2 gene in a Chinese patient with cleidocranial dysplasia. J Genet 97, 137–143 (2018). https://doi.org/10.1007/s12041-018-0891-2
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DOI: https://doi.org/10.1007/s12041-018-0891-2