Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia caused by runt-related transcription factor 2 (RUNX2
) mutations. In addition to the regular missense, small or large fragment deletions are the common mutation types of RUNX2
. This study aimed to find the rules of deletions in RUNX2
. The clinical information of one Chinese CCD family was collected. Genomic DNA was extracted for whole-exome sequencing (WES). Bioinformatics analyzed the pathogenicity of the variants. Polymerase chain reaction (PCR) and Sanger sequencing were carried out using specific primers. RT-PCR and Q-PCR were also used to detect the mRNA level of RUNX2
. The CCD studies related with deletions in RUNX2
from 1999 to 2021 from HGMD and PubMed were collected and analyzed for the relationship between the phenotypes and the length of deleted fragments. The proband presented typical CCD features, including delayed closure of cranial sutures, clavicle dysplasia, abnormal teeth. WES, PCR with specific primers and Sanger sequencing revealed a novel heterozygous 90-kbp deletion in RUNX2
(NG_008020.2 g.103671~193943), which caused a substitution (p.Asn183Ile) and premature termination (p.Asp184*). In addition, the mRNA expression of RUNX2
was decreased by 75.5% in the proband. Herein, 31 types of deletions varying from 2 bp to 800 kbp or covering the whole gene of RUNX2
were compared and the significant phenotypic difference was not found among these deletions. The CCD phenotypes were related with the final effects of RUNX2
mutation instead of the length of deletion. WES has the defects in identifying large indels, and direct PCR with specific primers and Sanger sequencing could make up for the shortcoming.
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