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Skeletal and molecular findings in 51 Cleidocranial dysplasia patients from Turkey
Author(s) -
Berkay Ezgi Gizem,
Elkanova Leyla,
Kalaycı Tuğba,
Uludağ Alkaya Dilek,
Altunoğlu Umut,
Cefle Kıvanç,
Mıhçı Ercan,
Nur Banu,
Taşdelen Elifcan,
Bayramoğlu Zuhal,
Karaman Volkan,
Toksoy Güven,
Güneş Nilay,
Öztürk Şükrü,
Palandüz Şükrü,
Kayserili Hülya,
Tüysüz Beyhan,
Uyguner Zehra Oya
Publication year - 2021
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.62261
Subject(s) - frontal bossing , cleidocranial dysplasia , short stature , brachycephaly , medicine , dysplasia , hypoplasia , haploinsufficiency , biology , anatomy , pathology , genetics , supernumerary , phenotype , skull , gene
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.