The present study searched for evidence of possible associations between some genetic factors that could affect the development of molar-incisor hypomineralisation (MIH). In 113 patients who were surgically treated at an Otorhinolaryngology and Cervicofacial Surgery Clinic (ORL) during early childhood, human leukocyte antigen (HLA) DQ2 and DQ8 haplotypes and single nucleotide polymorphisms (SNP) of eight amelogenesis-related genes were searched in genomic DNA. Genotypes were determined by high resolution melting (HRM), TaqMan genotyping assays, and Sanger sequencing. Association between MIH and the HLA DQ2 and DQ8 alleles was tested using a univariate logistic regression. The significance of genetic variants was analysed using the Cochran-Armitage tests for trend and the Fisher exact tests. We identified MIH in 22 (19.5 %) of the 113 children. Among the evaluated genetic variants, SNP rs2245803 in the MMP20 gene in a homozygous form in a recessive model was associated with MIH development (OR, 2.796; 95 %CI, 1.075 - 4.783; p = 0.0496) with the genotype distribution of TT(3), TG(6) or GG(13) in children with MIH and distribution of TT(18), TG(42) or GG(31) in children without MIH. While the aetiology of MIH remains unclear, our findings suggest that variants of genes associated with amelogenesis may play important roles in susceptibility to MIH.

The aims of the study were to identify craniofacial characteristics in patients with the rough hypoplastic amelogenesis imperfecta (AI) phenotype and to evaluate whether craniofacial variables are related to a mutation in either of the two genes associated with AI, enamelin (ENAM) and amelogenin (AMGX). Eight children (five males and three females) with rough hypoplastic AI phenotype, aged 6.5–15 years, from three families and their parents (three males and three females) were examined clinically, radiographically, and genetically. Seventeen variables were measured on lateral cephalometric radiographs in AI affected (n = 11) and AI unaffected (n = 3) members. Craniofacial measurements were statistically analysed using a Student's t-test. In all 14 individuals, mutation analysis of the ENAM and AMGX genes was performed by direct sequencing of the coding region. All AI affected patients had hypoplastic enamel with a rough surface and malocclusions. In the vertical plane, all AI children presented an anterior and/or posterior open bite (OB). Craniofacial analysis confirmed increased vertical relationships, with increased vertical jaw relationships and higher values for gonial angle. In two AI affected families, A and B, the same heterozygous ENAM g.8344delG mutation was confirmed, while in the third family, neither ENAM nor AMGX mutation was found. All patients with rough hypoplastic AI had a moderate to severe malocclusion with increased vertical dimensions regardless of the presence or absence of the ENAM g.8344delG mutation. As an OB requires appropriate timing of therapy, it is important to diagnose these patients as early as possible.