Phenotypic variability in LAMA3-associated amelogenesis imperfecta.
Phenotypic variability in LAMA3-associated amelogenesis imperfecta.
复制标题
LAMA3 相关的釉质形成不全的表型变异。
DOI：
10.1111/odi.14425
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发表时间：
2023
期刊：
影响因子：
3.8
通讯作者：
Hu,JanC-C
中科院分区：
文献类型：
--
作者：
Wang,Shih-Kai;Zhang,Hong;Wang,Yin-Lin;Seymen,Figen;Koruyucu,Mine;Simmer,JamesP;Hu,JanC-C
釉质发育异常（AI）是指遗传性釉质畸形。LAMA 3（laminin alpha-3）编码基底膜的关键蛋白组分（laminin-332）。携带异质性LAMA 3突变的个体先前已被证明具有局部釉质缺陷。本研究旨在确定临床表型和辨别遗传病因四AI kinkills.Materials和MethodsWhole‐exome分析进行搜索与疾病相关的序列变异，和微计算机断层扫描（μCT），以表征釉质deficiency.ResultsThe主要的釉质表型是广义薄釉质缺陷的坑和槽。还观察到发育不全釉质的水平带，伴有白垩白色变色和釉质矿化不足，并通过受影响牙齿的μCT分析证实。鉴定出4个致病LAMA 3突变（NM_198129.4：c.3712dup; c.5891dup; c.7367del; c.9400G > C）。在一个有较严重釉质缺损的先证者中也发现了复合异质性MMP 20突变（NM_004771.4：c.539A > G; c.692C > T），表明疾病表型的突变协同作用。结论LAMA 3基因的α3A（短）和α3B（长）异构体均是釉质形成所必需的。层粘连蛋白-332不仅对附着生长而且对釉质成熟至关重要。
ObjectiveAmelogenesis imperfecta (AI) is defined as inherited enamel malformations.LAMA3(laminin alpha‐3) encodes a critical protein component of the basement membrane (laminin‐332). Individuals carrying heterozygousLAMA3mutations have previously been shown to have localized enamel defects. This study aimed to define clinical phenotypes and to discern the genetic etiology for four AI kindreds.Materials and MethodsWhole‐exome analyses were conducted to search for sequence variants associated with the disorder, and micro‐computed tomography (μCT) to characterize the enamel defects.ResultsThe predominant enamel phenotype was generalized thin enamel with defective pits and grooves. Horizonal bands of hypoplastic enamel with chalky‐white discoloration and enamel hypomineralization were also observed and demonstrated by μCT analyses of affected teeth. Four disease‐causingLAMA3mutations (NM_198129.4:c.3712dup; c.5891dup; c.7367del; c.9400G > C) were identified. Compound heterozygousMMP20mutations (NM_004771.4:c.539A > G; c.692C > T) were also found in one proband with more severe enamel defects, suggesting a mutational synergism on disease phenotypes. Further analyses of the AI‐causing mutations suggested that both α3A (short) and α3B (long) isoforms of LAMA3 are essential for enamel formation.ConclusionsHeterozygousLAMA3mutations can cause generalized enamel defects (AI1A) with variable expressivity. Laminin‐332 is critical not only for appositional growth but also enamel maturation.