Expanding the phenotype of hypomaturation amelogenesis imperfecta due to a novel SLC24A4 variant.

OBJECTIVES: Biallelic variants in solute carrier family 24 member 4 (SLC24A4) have been previously reported to cause non-syndromic autosomal recessive amelogenesis imperfecta (AI) of the pigmented hypomaturation type (MIM #615887). We here describe a novel variant in SLC24A4 causing mild enamel hypomaturation defects also in heterozygous individuals. MATERIALS AND METHODS: In the present pedigree analysis, a large consanguineous Syrian family with AI of the hypomaturation type was investigated by clinical and dental evaluation, and exome and Sanger sequencing. Dental histological investigations of seven primary and two permanent teeth were performed. RESULTS: Homozygous variants in SLC24A4 (c.1604G>A; p.Gly535Asp) were identified in five individuals with brown discolorations and irregular pits and grooves of the teeth. Severe attritions, occlusal abfractions, and the radiological lack of contrast between enamel and dentin point out a mineralization defect. Histological dental investigations confirmed the clinical diagnosis of AI of the hypomaturation type. In two heterozygous individuals, a mild hypomaturation defect was present with white and light brown enamel discolorations. CONCLUSIONS: This is the first report of heterozygous SLC24A4 variants causing mild hypomaturation defects, providing confirmatory evidence that the function of SLC24A4 in calcium transport has a crucial role in the maturation stage of amelogenesis. CLINICAL RELEVANCE: The present report is expanding the clinical phenotype of SLC24A4 variants to more severe forms of amelogenesis imperfecta. An autosomal-dominant inheritance pattern with mild clinical phenotypes in heterozygotes has to be considered.