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.

中文翻译：

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由于新的SLC24A4变异，扩大了发育不全性发育不全的表型。

目的先前已报道了溶质载体家族24成员4（SLC24A4）中的双等位基因变体引起色素性早熟类型（MIM＃615887）的非综合征性常染色体隐性釉质发育不全（AI）。我们在这里描述SLC24A4中的一种新变异，也会在杂合子个体中引起轻度珐琅质过早成熟缺陷。材料与方法在本系谱分析中，通过临床和牙齿评估以及外显子组和Sanger测序研究了一个血统不足的叙利亚血统叙利亚大家庭。对7颗乳牙和2颗恒牙进行了牙齿组织学检查。结果SLC24A4的纯合变异（c.1604G> A； p.Gly535Asp）在5个个体中鉴定为褐色变色，牙齿上有不规则的凹坑和凹槽。严重的磨损，牙合畸形，牙釉质和牙本质之间缺乏放射线对比，这表明存在矿化缺陷。牙科组织学研究证实了早熟型AI的临床诊断。在两个杂合的个体中，存在轻度的早熟缺陷，白色和浅棕色搪瓷变色。结论这是导致轻度早熟缺陷的杂合SLC24A4变体的首次报道，提供了证实性证据，表明SLC24A4在钙转运中的功能在促成釉的成熟阶段中起着至关重要的作用。临床相关性本报告将SLC24A4变体的临床表型扩展到更严重的牙釉质形成不全形式。必须考虑杂合子中具有轻度临床表型的常染色体显性遗传模式。