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

BMC Medical Genetics

卷:20

Kazuyoshi Hosomichi¹  Masayuki Tanaka²  Minoru Kimura³  Rena Kojima⁴  Hiroshi Yamazaki⁴  Masahiro Uchibori⁵  Ken-ichi Aoyama⁵  Yoshihide Ota⁵  Yuko Osawa⁵  Gen Nishimura⁶  Shiro Yamada⁷ 

[1] Department of Bioinformatics and Genomics, Kanazawa University;

[2] Department of Bioinformatics, Support Center for Medical Research and Education, Tokai University School of Medicine;

[3] Department of Molecular Life Science, Tokai University School of Medicine;

[4] Department of Oral and Maxillofacial Surgery, Tokai University Oiso Hospital;

[5] Department of Oral and Maxillofacial Surgery, Tokai University School of Medicine;

[6] Department of Pediatric Imaging, Tokyo Metropolitan Children’s Medical Center;

[7] Department of Pediatrics, Tokai University Oiso Hospital;

关键词: Local osteodysplasia;    Oral and maxillofacial bones;    PCNT;    Pericentrin;    Whole exome sequencing;   

DOI  :  10.1186/s12881-019-0858-z

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown