MSX1 variant causes nonsyndromic tooth agenesis in a Japanese patient

Abstract MSX1 variants are associated with autosomal dominant craniofacial developmental anomalies, including congenital tooth agenesis. Here, whole-exome sequencing in a Japanese patient with congenital tooth agenesis identified a novel de novo heterozygous frameshift variant in MSX1 (NM_002448.3:c.299delC). The variant is predicted to generate a truncated protein, p.(Pro100Argfs*60), that lacks the C-terminal region of MSX1 and is expected to result in loss of function. The patient presented with congenital tooth agenesis, including canine agenesis. Taken together with the genetic findings, this case supports the involvement of MSX1 in congenital tooth agenesis and broadens the reported phenotypic presentation of MSX1-related tooth agenesis. This report adds to the spectrum of disease-associated MSX1 variants and supports the utility of genomic testing for molecular diagnosis in rare dental developmental anomalies.