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.

Microcephalic osteodysplastic primordial dwarfism type II: Additional nine patients with implications on phenotype and genotype correlation

“…We noted that the two sibs of Family 7 who had the acceptor splice site variant displayed congenitally missing tooth (five and three missing permanent tooth in Patients 9 and 8, respectively) as well as short rooted teeth. Interestingly, the heterozygous missense variant in the PCNT have shown maxillofacial osteodysplasia in a single patient and to increase the susceptibility to intracranial aneurysms (Aoyama et al, 2019; Lorenzo‐Betancor et al, 2018)…”

The PCM scaffold enables RNA localization to centrosomes

“…Human PCNT and Drosophila Pcnt-like protein (Plp) share functionally conserved roles in PCM scaffolding and microtubule nucleation [23][24][25][26][27][28]. In humans, loss-of-function PCNT mutations are associated with microcephalic osteodysplastic primordial dwarfism type II (MOPD II), as well as cardiac and neurovascular abnormalities [29][30][31][32][33]. Loss of Drosophila Plp also leads to pleiotropic effects, including embryonic lethality, neuronal dysfunction, and sterility [24,25,28,34].…”