China Journal of Oral and Maxillofacial Surgery ›› 2022, Vol. 20 ›› Issue (4): 360-365.doi: 10.19438/j.cjoms.2022.04.008

• Original Articles • Previous Articles     Next Articles

Identification of a de novo mutation in ANO5 by whole exome sequencing and clinical phenotype of familial gigantiform cementoma

LI Xin, WANG Zhou-yang, QIN Xing-jun   

  1. Department of Oromaxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology. Shanghai 200011, China
  • Received:2021-11-29 Revised:2022-02-28 Online:2022-07-20 Published:2022-08-02

Abstract: PURPOSE: To develop an approach based on whole exome sequencing (WES) to explore the correlation between genotype and clinical phenotype of a Chinese familial gigantiform cementoma (FGC) family caused by a mutation in ANO5 gene. METHODS: Nine patients from a Chinese FGC family with facial deformities and lower limb fractures were included. The clinical manifestations, skeletal radiographic features, bone mineral density (BMD), and bone turnover biomarkers were investigated. Peripheral blood from 9 patients and 14 controls within the family was collected, and WES was performed. By using filtering strategy, the candidate genes were sequenced and further validated by PCR and Sanger sequencing in the unaffected individuals within the family and 384 healthy control subjects. RESULTS: The major manifestations of Chinese FGC patients were representative multiquadrant and expansive deformities involving the mandible and maxilla, especially severe in the anterior mandible with diffuse osteopenia bone loss and several fractures in the lower limbs. Sequencing results showed that there was a missense, heterozygous mutation in ANO5 (c.1538C>T, p.Thr513Ile) in all affected individuals, that affected the folding, structure and function of ANO5. CONCLUSIONS: FGC is a rare autosomal dominant hereditary disease caused by ANO5 mutations, with severe facial deformity, long bone fractures and low BMD as main characteristics of Chinese' patients. The first and a novel missense mutation of ANO5 was identified, which extended the phenotypic and genetic spectrum of FGC.

Key words: Familial gigantiform cementoma, ANO5 gene, Novel mutation, Phenotype, Genotype

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