Skeletal and molecular findings in 51 Cleidocranial dysplasia patients from Turkey

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Berkay E. G., Elkanova L., Kalayci T., Uludağ Alkaya D., Altunoglu U., Cefle K., ...Daha Fazla

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, cilt.185, sa.8, ss.2488-2495, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 185 Sayı: 8
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1002/ajmg.a.62261
  • Dergi Adı: AMERICAN JOURNAL OF MEDICAL GENETICS PART A
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source, BIOSIS, CAB Abstracts, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.2488-2495
  • Anahtar Kelimeler: bell&#8208, shaped thorax, clavicle, Cleidocranial dysplasia, RUNX2, MUTATION ANALYSIS, RUNX2 MUTATION, GENE, DEFICIENCY, PROMOTER, DENSITY
  • Akdeniz Üniversitesi Adresli: Evet

Özet

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.