Identification of a novel mutation of RUNX2 in a family with cleidocranial dysplasia by whole-exome sequencing

Authors

• Dan Ma
• Jun Zhang
• Tao Cai
• RD Leapman

Abstract

The RUNX2 gene is well known for its crucial role in osteoblasts differentiation and chondrocytes maturation. Previous studies have shown that mutations in RUNX2 contribute to cleidocranial dysplasia (CCD; OMIM 119600). CCD is an autosomal dominant inheritable skeletal disorder and characterized by delayed closure of the cranial sutures, hypoplastic clavicles, short stature, supernumerary teeth, delayed eruption or impaction of permanent teeth and other skeletal malformations. In the present study, two patients in a family with CCD and tricuspid regurgitation were recruited for genetic analysis. Whole exome sequencing was performed to identify the disease-causing mutation. A novel mutation of RUNX2 (c.C473>A; p.A158>E) was identified in both patients but not in normal family members. This mutation was further confirmed by Sanger sequencing and predicted to be deleterious by several commonly used algorithms, such as SIFT, PPT-2 and MutationTaster. This finding extended the mutation spectrum and clinical features of CCD and facilitated clinic diagnosis and genetic counseling.

Scientific Focus Area: Genetics and Genomics

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