Primary failure of eruption: Clinical and genetic findings in the mixed dentition

Abstract

Objective: To test the hypothesis that mutations in the parathyroid hormone 1 receptor ( PTH1R) include effects in both primary and permanent teeth.

Materials and methods: DNA was extracted from saliva samples of 29 patients (8 familial and 21 sporadic) who presented with clinical evidence of infraoccluded teeth, and their unaffected relatives (N = 22). Sequencing followed by mutational analysis of the coding regions of PTH1R gene was completed for all individuals (N = 29).

Results: Eight of 29 cases revealed a heterozygous pathogenic variant in the PTH1R gene; five of eight variants represented distinct mutations based on comparison with the dbSNP, HGMD, and ESP databases. One mutation (c.1765 T>C p.Trp89Arg) was found to segregate within a family (n = 3). In silico analyses for all variants revealed a putative pathogenic effect. A genotype-phenotype correlation was reported as defined by a functional mutation in PTH1R and corresponding effects on one or more posterior teeth only; unilateral or bilateral involvement, infraoccluded primary teeth.

Conclusions: Novel mutations were reported in the PTH1R gene that included PFE-affected primary molars, thus providing the basis for using a genetic diagnostic tool for early diagnosis leading to proper management.

Keywords: Dental eruption; PTH1R; Primary failure of eruption (PFE).

Figure 1.

(A, B) Intraoral photos of two brothers. Panoramic: variant downstream of exon 5 (CTCF Binding site) rs113566258 SNP c.313+32 A>G; variant in exon 16 (position 3:46903467) c.1593-95 Del C, p.531/532; synonymous variant in exon 10 (position 3:46899419) c.1152 G>A.

Figure 2.

Intraoral photos. Panoramic: synonymous variant in exon 10 (position 3:46899419) c.1152 G>A.

Figure 3.

(A, B) Intraoral photos of two brothers. Panoramic: familial missense variant in exon 16 c.1765 T>C p.589 W>R.