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CC BY 4.0 · Glob Med Genet 2022; 09(01): 023-028
DOI: 10.1055/s-0041-1736482
Original Article

Rare Findings in Cleidocranial Dysplasia Caused by RUNX Mutation

Aysel Kalayci Yigin 
1   Department of Medical Genetics, Istanbul University-Cerrahpaşa, Cerrahpaşa Medical School, Istanbul, Turkey
,
Mehmet Bugrahan Duz 
2   Department of Medical Genetics, Health Sciences University, Haseki Training and Research Hospital, Istanbul, Turkey
,
Mehmet Seven 
1   Department of Medical Genetics, Istanbul University-Cerrahpaşa, Cerrahpaşa Medical School, Istanbul, Turkey
› Author Affiliations Funding None.
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Abstract

Background Cleidocranial dysplasia (CCD, #MIM119600) is an autosomal-dominant skeletal dysplasia characterized by delayed closure of the cranial sutures, aplasia, or hypoplasia of the clavicles and dental abnormalities. These findings were accompanied by mobile and drooping shoulders, frontal and parietal bossing, hypertelorism, brachycephaly, short stature, supernumerary, and late erupting teeth. Radiographic studies can reveal involvement of multiple bones including skull, chest, pelvis, and limbs. CCD can be diagnosed with clinical and radiological evaluation and validated by molecular studies. Heterozygous loss of function RUNX2 gene, which plays an important role in osteogenesis and differentiation of precursor cells, causes CCD phenotype.

Methods In this article, we reported five cases from three unrelated families with CCD phenotype. All exons and exonic–intronic boundary regions of RUNX2 gene from five patients were analyzed by polymerase chain reaction amplification and direct Sanger-sequencing.

Results Our patients had classical CCD phenotype and we detected three different previously described mutations including c.1171C > T, IVS4 + 4delAAGT and c.676G > A. However, nail dysplasia has never been associated with these mutations. Our patients had varying degrees of nail dysplasia. Two of three mutations are related with Runt DNA-binding domain of RUNX2 protein in Wnt signaling and c.1171C > T had effect on proline/serine/threonine-rich (PST) domain. Recently, Wnt signaling pathway was presented as a key regulator of digit and nail differentiation. Our data suggest that RUNX2 gene may have an essential role on embryogenesis of nails, probably by protecting their integrity.

Keywords

cleidocranial dysplasia - RUNX mutation - Sanger sequencing - rare findings

Ethical Approval

This research has been approved by the IRB of the authors' affiliated institutions and conducted in accordance with the Declaration of Helsinki.


Note

Written informed consent has been obtained from the patient(s) to publish this paper.


Data Availability Statement

Data available on request due to restrictions privacy or ethical. The data presented in this study are available on request from the corresponding author.




Publication History

Received: 05 July 2021

Accepted: 31 August 2021

Article published online:
22 October 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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