Department of Pediatric Dentistry & Dental Research Institute, School of Dentistry, Seoul National University, 275-1 Yongon-dong, Chongno-gu, Seoul 110-768, Korea.
J Dent Res. 2013 Oct;92(10):899-904. doi: 10.1177/0022034513502054. Epub 2013 Aug 19.
Amelogenesis imperfecta (AI) can be either isolated or part of a larger syndrome. Junctional epidermolysis bullosa (JEB) is a collection of autosomal-recessive disorders featuring AI associated with skin fragility and other symptoms. JEB is a recessive syndrome usually caused by mutations in both alleles of COL17A1, LAMA3, LAMB3, or LAMC2. In rare cases, heterozygous carriers in JEB kindreds display enamel malformations in the absence of skin fragility (isolated AI). We recruited two kindreds with autosomal-dominant amelogenesis imperfecta (ADAI) characterized by generalized severe enamel hypoplasia with deep linear grooves and pits. Whole-exome sequencing of both probands identified novel heterozygous mutations in the last exon of LAMB3 that likely truncated the protein. The mutations perfectly segregated with the enamel defects in both families. In Family 1, an 8-bp deletion (c.3446_3453del GACTGGAG) shifted the reading frame (p.Gly 1149Glufs8). In Family 2, a single nucleotide substitution (c.C3431A) generated an in-frame translation termination codon (p.Ser1144). We conclude that enamel formation is particularly sensitive to defects in hemidesmosome/basement-membrane complexes and that syndromic and non-syndromic forms of AI can be etiologically related.
釉质发育不全（AI）可以是孤立的，也可以是更大综合征的一部分。交界性大疱性表皮松解症（JEB）是一组常染色体隐性遗传疾病，其特征是 AI 与皮肤脆弱和其他症状有关。JEB 是一种隐性综合征，通常由 COL17A1、LAMA3、LAMB3 或 LAMC2 的两个等位基因突变引起。在极少数情况下，JEB 家系中的杂合子携带者在没有皮肤脆弱的情况下表现出牙釉质畸形（孤立性 AI）。我们招募了两个常染色体显性釉质发育不全（ADAI）家系，其特征为广泛严重的釉质发育不全，伴有深线性凹槽和凹陷。对两个先证者的全外显子组测序发现了 LAMB3 最后一个外显子中的新杂合突变，这些突变可能导致蛋白截断。这些突变在家系 1 和家系 2 中与牙釉质缺陷完全分离。在家族 1 中，存在 8 个碱基对的缺失（c.3446_3453del GACTGGAG），导致阅读框移位（p.Gly 1149Glufs8）。在家族 2 中，存在一个单核苷酸取代（c.C3431A），导致无义翻译终止密码子（p.Ser1144）。我们得出结论，牙釉质形成对半桥粒/基底膜复合物缺陷特别敏感，并且综合征性和非综合征性 AI 形式可能具有病因学相关性。
