Skeletal and molecular findings in 51 Cleidocranial dysplasia patients from Turkey

Berkay E. G., Elkanova L., Kalayci T., ULUDAĞ ALKAYA D., Altunoglu U., Cefle K., ...More

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, vol.185, no.8, pp.2488-2495, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 185 Issue: 8
  • Publication Date: 2021
  • Doi Number: 10.1002/ajmg.a.62261
  • Journal Name: AMERICAN JOURNAL OF MEDICAL GENETICS PART A
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source, BIOSIS, CAB Abstracts, EMBASE, MEDLINE
  • Page Numbers: pp.2488-2495
  • Keywords: bell&#8208, shaped thorax, clavicle, Cleidocranial dysplasia, RUNX2, MUTATION ANALYSIS, RUNX2 MUTATION, GENE, DEFICIENCY, PROMOTER, DENSITY
  • Istanbul University Affiliated: Yes

Abstract

Loss or decrease of function in runt-related transcription factor 2 encoded by RUNX2 is known to cause a rare autosomal-dominant skeletal disorder, cleidocranial dysplasia (CCD). Clinical spectrum and genetic findings in 51 CCD patients from 30 unrelated families are herein presented. In a majority of the patients, facial abnormalities, such as delayed fontanel closure (89%), parietal and frontal bossing (80%), metopic groove (77%), midface hypoplasia (94%), and abnormal mobility of shoulders (90%), were recorded following clinical examination. In approximately one-half of the subjects, wormian bone (51%), short stature (43%), bell-shaped thorax (42%), wide pubic symphysis (50%), hypoplastic iliac wing (59%), and chef's hat sign (44%) presented in available radiological examinations. Scoliosis was identified in 28% of the patients. Investigation of RUNX2 revealed small sequence alterations in 90% and gross deletions in 10% of the patients; collectively, 23 variants including 11 novel changes (c.29_30insT, c.203delAinsCG, c.423 + 2delT, c.443_454delTACCAGATGGGAinsG, c.505C > T, c.594_595delCTinsG, c.636_637insC, c.685 + 5G > A, c.1088G > T, c.1281delC, Exon 6-9 deletion) presented high allelic heterogeneity. Novel c.29_30insT is unique in affecting the P1-driven long isoform of RUNX2, which is expected to disrupt the N-terminal region of RUNX2; this was shown in two unrelated phenotypically discordant patients. The clinical findings highlighted mild intra-familial genotype-phenotype correlation in our CCD cohort.