Novel MSX1 variants identified in families with nonsyndromic oligodontia

• Published in: International journal of oral science Vol. 13; no. 1; p. 2
• Main Authors: Zheng, Jinglei, Yu, Miao, Liu, Haochen, Cai, Tao, Feng, Hailan, Liu, Yang, Han, Dong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08-01-2021; Springer Nature B.V; Nature Publishing Group
• Subjects: 631/208; 692/699; Anodontia - genetics; Bioinformatics; Dentistry; Genetic counseling; Humans; Localization; Medicine; MSX1 Transcription Factor - genetics; Oral and Maxillofacial Surgery; Orthopedics; Pedigree; Surgical Orthopedics; Whole Exome Sequencing
• ISSN: 1674-2818; 2049-3169
• DOI: 10.1038/s41368-020-00106-0

The goal of this study was to identify
MSX1
gene variants in multiple Chinese families with nonsyndromic oligodontia and analyse the functional influence of these variants. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variants in five families with nonsyndromic oligodontia, and a series of bioinformatics databases were used for variant confirmation and functional prediction. Phenotypic characterization of the members of these families was described, and an in vitro analysis was performed for functional evaluation. Five novel
MSX1
heterozygous variants were identified: three missense variants [c.662A>C (p.Q221P), c.670C>T (p.R224C), and c.809C>T (p.S270L)], one nonsense variant [c.364G>T (p.G122*)], and one frameshift variant [c.277delG (p.A93Rfs*67)]. Preliminary in vitro studies demonstrated that the subcellular localization of MSX1 was abnormal with the p.Q221P, p.R224C, p.G122*, and p.A93Rfs*67 variants compared to the wild type. Three variants (p.Q221P, p.G122*, and p.A93Rfs*67) were classified as pathogenic or likely pathogenic, while p.S270L and p.R224C were of uncertain significance in the current data. Moreover, we summarized and analysed the
MSX1
-related tooth agenesis positions and found that the type and variant locus were not related to the severity of tooth loss. Our results expand the variant spectrum of nonsyndromic oligodontia and provide valuable information for genetic counselling.