Cleidocranial dysplasia with a rare mutation: Study of a family with review of literature

Abstract

Introduction: The present study was aimed at advancing the understanding of the pathogenesis of cleidocranial dysplasia (CCD) by presenting a case study based on history, physical examination, typical radiological features, and molecular analysis and a review of the literature. Methods: This study began with a 23-year-old boy (proband) who was referred to the department of oral and maxillofacial radiology with chief complaint of the upper-left first molar tooth and routine dental examination. While evaluating the panoramic radiograph, the patient had approximately 57 teeth in his both of the jaws. Clinical, radiographical and molecular features of the proband, two siblings and their parents were examined and then, DNA analysis was performed. Results: Overall, we present 3 CCD patients with a mutation in the VWRPY motif. The deletion of c. 1754_1757 delTTTG (NM_001024630.2) is determined and it leads to a frame shift mutation and stop codon, p. V585Gfs56X. Conclusions: The present study emphasized the importance of further clinical and molecular investigation when even a single case of CCD is identified within a family. This is the first study performed in Turkey about a family with a mutation in the VWRPY motif. Genotype-phenotype association studies in individuals with CCD are necessary to provide important insights into molecular mechanisms associated with this disease.

Identification of a Novel Splice Site Mutation in RUNX2 Gene in a Family with Rare Autosomal Dominant Cleidocranial Dysplasia

“…Mice carrying one disrupted RUNX2 allele resembled the human CCD phenotype, including clavicular hypoplasia, and the homozygous Runx2 mutant mice revealed disturbing bone formation due to the absence of ossification [17] . Until now, over 100 different mutations [19] have been reported in the RUNX2 gene [20][21][22] , including missense, nonsense, splicing, and frameshift variants in over 65% of CCD cases [21][22][23] . In this study, a novel splice site mutation of c.860-2A>G in the RUNX2 gene was identified.…”

“…In this study, a novel splice site mutation of c.860-2A>G in the RUNX2 gene was identified. RUNX2 contains several domains: (i) an N-terminal Q/A domain composed of a stretch of 23 consecutive glutamines, followed by 17 consecutive alanines, which the length of this domain is important for transcriptional activity [24][25][26] ; (ii) a RUNT domain, that has a unique ability of mediating DNA binding and protein heterodimerization; (iii) a C-terminal proline-serinethreonine-rich activation domain that can also mediate protein-protein interaction [24] and it is essential for the transcriptional activity of RUNX2 protein [23] ; (iv) the last five amino acids of the protein known as the VWPRY motif [19] .…”

Identification of a novel RUNX2 gene mutation and early diagnosis of CCD in a cleidocranial dysplasia suspected Iranian family

“…Cleidocranial dysplasia (CCD) is an autosomal dominant (AD) skeletal dysplasia which is also known as Marie and Sainton disease. 1,2 This disease consists of the condition including defective skull ossification, open fontanels, clavicular hypoplasia, delayed ossification of the pelvis, the late eruption of permanent teeth, malformed dental roots, and supernumerary teeth. [3][4][5][6][7][8] Although the intelligence of CCD affected individuals is normal, these patients suffer from their appearance characteristics related to the disturbance in the growth of the involved bones.…”

“…Cleidocranial dysplasia (CCD) is an autosomal dominant (AD) skeletal dysplasia which is also known as Marie and Sainton disease 1,2 . This disease consists of the condition including defective skull ossification, open fontanels, clavicular hypoplasia, delayed ossification of the pelvis, the late eruption of permanent teeth, malformed dental roots, and supernumerary teeth 3‐8 .…”

Cleidocranial dysplasia: Two unique cases

“…Gardner syndrome, Hallerman-Streiff syndrome (narrow face, hypotrichosis, mi-crophthalmia), [15] hypohidrotic ectodermal dysplasia (hypohidrosis, anomalous dentition, onychodysplasia, and hypotrichosis), focal dermal hypoplasia (relative focal absence of the dermis, skin atrophy, streaky pigmentation, multiple mucosal papillomas, and deformity of the extremities), apert syndrome (craniosynostosis, craniofacial abnormalities and symmetrical syndactly of the hands and feet), and craniofacial dysostosis (premature craniosynostosis with other abnormalities). [6] Complications CCD may show complications such as pes planus, genu velgum, shoulder and hip dislocation, recurrent sinus and ear infections, upper airway complications, hearing loss, dental caries, osteomyelitis of jaws, and respiratory distress in infants.…”