Mutations of MSX1 have been associated with nonsyndromic hypodontia. To seek the causal gene mutation sites in a family with nonsyndromic oligodontia, whole‐exome sequencing (WES) was performed to seek the causative locus of the family. The candidate mutation was further identified by Sanger sequencing afterward. Two mutations of MSX1 were found both in the proband and her mother. One novel heterozygous missense mutation (c.C667G, p.R223G) of MSX1 inherited from the asymptomatic mother with mosaic mutation was located in the highly conserved fragment of exon 2. The other was a synonymous mutation (c.C348T, p.G116G) in exon 1, which had been reported. The novel maternal heterozygous missense mutation (c.C667G, p.R223G) was likely to be the major reason for nonsyndromic oligodontia in the family. This is the first mosaic variant that has been recorded of the MSX1 gene. Our study expands the phenotype–genotype correlation associated with MSX1 variants. Our study also suggests that the determination of the mosaicism is essential for precise genetic counseling if a disease appears to arise de novo.

中文翻译：

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从母体嵌合体遗传的 MSX1 新突变导致严重影响儿童的非综合征性少牙症

MSX1 的突变与非综合征性牙齿不全有关。为了在非综合征性少牙症家族中寻找致病基因突变位点，进行全外显子组测序（WES）以寻找该家族的致病基因座。之后通过 Sanger 测序进一步鉴定了候选突变。在先证者和她的母亲身上都发现了两个 MSX1 突变。MSX1 的一个新的杂合错义突变 (c.C667G, p.R223G) 位于外显子 2 的高度保守片段中，来自无症状母亲的镶嵌突变的 MSX1。另一个是同义突变 (c.C348T, p.G116G)在外显子 1 中，已报道。新的母体杂合错义突变（c.C667G，p.R223G）可能是该家族中非综合征性少牙症的主要原因。这是第一个记录到的 MSX1 基因镶嵌变异体。我们的研究扩展了与 MSX1 变异相关的表型-基因型相关性。我们的研究还表明，如果疾病似乎是从头出现的，那么确定嵌合体对于精确的遗传咨询至关重要。