Amelogenesis imperfecta phenotype-genotype correlations with two amelogenin gene mutations
Amelogenesis imperfecta phenotype-genotype correlations with two amelogenin gene mutations
复制标题
DOI：
10.1016/s0003-9969(02)00003-1
复制
发表时间：
2002-04-01
影响因子：
3
通讯作者：
Wright, JT
中科院分区：
文献类型：
--
作者：
Hart, PS;Aldred, MJ;Wright, JT
釉原蛋白是牙釉质发育中的主要基质蛋白，被认为是正常釉质形成所必需的，但其确切功能尚不清楚。编码釉原蛋白的AMELX基因的突变导致X连锁的釉质发生缺失（AI），其表型特征为发育不全和/或矿化不良的釉质。迄今为止，已经报道了八种不同的AMELX缺失和置换突变。本研究的目的是评估两个大的分离的X连锁AI的基因型和表型。表型受影响的男性在家庭1有黄褐色，矿化不良的釉质;那些在家庭2有薄，光滑，发育不全的釉质。在这两个kindly杂合子女性有垂直发育不全的沟在他们的牙釉质。从家族成员中获得DNA;扩增AMELX的外显子1-7并测序。家族1的突变分析揭示了在核苷酸256处A -> T的单碱基对改变，导致His -> Leu改变。家族2的分析揭示了密码子119中的C-核苷酸的缺失，导致接下来的6个密码子的移码改变，以及导致比野生型短18个氨基酸的蛋白质的截短的过早终止密码子。迄今为止，所有改变釉原蛋白C-末端第157位氨基酸后的突变都导致发育不良表型。相比之下，其他AMELX突变似乎主要导致矿化缺陷（例如在家族1中观察到的突变）。这种差异表明正常釉原蛋白的C-末端对于控制釉质厚度是重要的。(C)2002爱思唯尔科技有限公司版权所有。
Amelogenin, the predominant matrix protein in developing dental enamel, is considered essential for normal enamel formation, but its exact functions are undefined. Mutations in the AMELX gene that encodes for amelogenin protein cause X-linked amelogenesis imperfecta (AI), with phenotypes characterized by hypoplastic and/or poorly mineralized enamel. Eight different AMELX deletion and substitution mutations have been reported to date. The purpose here was to evaluate the genotype and phenotype of two large kindreds segregating for X-linked AI. Phenotypically affected males in family 1 had yellowish-brown, poorly mineralized enamel; those in family 2 had thin, smooth, hypoplastic enamel. Heterozygous females in both kindreds had vertical hypoplastic grooves in their enamel. DNA was obtained from family members; exons 1-7 of AMELX were amplified and sequenced. Mutational analysis of family 1 revealed a single-base-pair change of A --> T at nucleotide 256, resulting in a His --> Leu change. Analysis of family 2 revealed deletion of a C-nucleotide in codon 119 causing a frameshift alteration of the next six codons, and a premature stop codon resulting in truncation of the protein 18 amino acids shorter than the wild-type. To date, all mutations that alter the C-terminus of amelogenin after the 157th amino acid have resulted in a hypoplastic phenotype. In contrast, other AMELX mutations appear to cause predominantly mineralization defects (e.g. the mutation seen in family 1). This difference suggests that the C-terminus of the normal amelogenin protein is important for controlling enamel thickness. (C) 2002 Elsevier Science Ltd. All rights reserved.