Abstract

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.

Highlights

  • Congenital tooth agenesis (TA) is one of the most common dental anomalies and may lead to masticatory dysfunction, speech alteration, aesthetic problems, and malocclusion.[1]

  • Clinical findings and variant detection The TA patterns and pedigrees of five Chinese families are shown in Figs. 1 and 2

  • Novel muscle segment homeobox 1 (MSX1) variants identified in families with nonsyndromic oligodontia Zheng et al

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Summary

1234567890();,: INTRODUCTION

Congenital tooth agenesis (TA) is one of the most common dental anomalies and may lead to masticatory dysfunction, speech alteration, aesthetic problems, and malocclusion.[1]. This study aimed to continue to expand the variant spectrum of MSX1 associated with nonsyndromic oligodontia, explore the functional impacts of the identified novel variant loci, and analyse the genotype–phenotype correlations

RESULTS
II-2 Normal
METHODS

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