In:
American Journal of Medical Genetics Part A, Wiley, Vol. 185, No. 8 ( 2021-08), p. 2488-2495
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.
Type of Medium:
Online Resource
ISSN:
1552-4825
,
1552-4833
DOI:
10.1002/ajmg.a.v185.8
DOI:
10.1002/ajmg.a.62261
Language:
English
Publisher:
Wiley
Publication Date:
2021
detail.hit.zdb_id:
1493479-6
SSG:
12
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