New PCNT candidate missense variant in a patient with oral and maxillofacial osteodysplasia: a case report

Abstract

Background: Osteodysplasia of the oral and maxillofacial bone is generally accompanied by systemic bone abnormalities (such as short stature, joint contracture) or other systemic abnormalities (such as renal, dermatological, cardiovascular, optic, or hearing disorders). However, it does not always present this way. Recent reports have suggested that genome-wide sequencing is an effective method for identifying rare or new disorders. Here, we performed whole-exome sequencing (WES) in a patient with a unique form of acquired, local osteodysplasia of the oral and maxillofacial region.

Case presentation: A 46-year-old woman presented to our hospital with the complaint of gradually moving mandibular teeth (for 6 months), changing facial appearance, and acquired osteolysis of the oral and maxillofacial bones, showing mandibular hypoplasia without family history. Upon skeletal examination, there were no abnormal findings outside of the oral and maxillofacial area; the patient had a height of 157 cm and bone mineral density (according to dual energy x-ray absorptiometry) of 90%. Results of blood and urine tests, including evaluation of bone metabolism markers and neurological and cardiovascular examinations, were normal. We performed WES of genomic DNA extracted from the blood of this patient and her mother, who did not have the disease, as a negative control. We identified 83 new missense variants in the patient, not detected in her mother, including a candidate single nucleotide variant in exon 14 of PCNT (pericentrin). Critical homozygous or compound heterozygous variants in PCNT are a known cause of microcephalic osteodysplastic primordial dwarfism type II accompanied by mandibular hypoplasia, which is similar to the maxillofacial phenotype in this patient.

Conclusions: Protein simulations performed using Polymorphism Phenotyping v2 and Combined Annotation Dependent Depletion software indicated that this missense variant is likely to disrupt the PCNT protein structure. These results suggest that this is a new form of osteolysis related to this PCNT variant.

Keywords: Local osteodysplasia; Oral and maxillofacial bones; PCNT; Pericentrin; Whole exome sequencing.

Fig. 1

Patient imaging data. a Photographs from extraoral examination reveal mandibular hypoplasia but no asymmetry. b Photographs from intraoral examination reveal an anterior open bite (inter-incisor distance: 23 mm) and early contact of the second molars. The upper teeth are crowded without a cleft palate; the lower teeth are not crowded

Fig. 2

X-ray images. a Posteroanterior and lateral skull views do not reveal morphological abnormalities of the head or face height and width. b A panoramic radiographic image shows axial and coronal thinning of the alveolar bone in the maxilla and the entire mandibular (condyle, angle, body, and alveolar) bone

Fig. 3

Computed tomography imaging. Imaging shows axial and coronal thinness of the alveolar bone, anterior wall of the maxillary sinus in the maxilla, and the entire mandibular (condyle, angle, body, and alveolar) bone

Fig. 4

99mTc bone scintigraphy shows tracer uptake in the maxillary and mandibular bones

Fig. 5

Missense variant present in exon 14. The variant was determined to be PCNT: NM_006031, exon 14, c.T2515C, p.C839R; NM_001315529, exon 14, c.T2161C, p.C721R. a Sanger sequencing results for the patient and her mother. b Mutation map of two isoforms (transcript variants)