Dentinogenesis imperfecta 1 with or without progressive hearing loss is associated with distinct mutations in DSPP
Dentinogenesis imperfecta 1 with or without progressive hearing loss is associated with distinct mutations in DSPP
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DOI：
10.1038/84848
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发表时间：
2001-02-01
期刊：
影响因子：
30.8
通讯作者：
Kong, XY
中科院分区：
文献类型：
--
作者：
Xiao, SX;Yu, C;Kong, XY
牙本质发育不全1(DGI1，MIM 125490)是一种以牙本质生成和矿化异常为特征的常染色体显性遗传性牙病。DGI1基因座最近在4q21(参考文献)上被细化到2-Mb区间。1)。在这里，我们研究了三个携带DCI1的中国家庭。我们发现两个家系的受累个体也表现出进行性感音神经性高频听力损失(基因DfNA39)。我们在这三个家庭中发现了牙本质涎磷蛋白基因(DSPP)中的三个疾病特异性突变。在一个没有DFNA39的家系中，我们在内含子3的供体剪接点检测到G->；A转换，该突变预计会导致外显子3的跳过。然而，在另外两个同时感染DGI1和DFNA39的家系中，我们分别在DSPP的外显子a和3中发现了两个独立的核苷酸颠换。这会导致蛋白质跨膜区预测的两个相邻氨基酸残基的错义突变。此外，先前报道的在牙齿(2)中特异表达的DSPP的转录本也在小鼠的内耳中被检测到。因此，我们首次证明了DSPP的不同突变是DGI1临床表现的原因，无论有没有DFNA39。
Dentinogenesis imperfecta 1 (DGI1, MIM 125490) is an autosomal dominant dental disease characterized by abnormal dentin production and mineralization. The DGI1 locus was recently refined to a 2-Mb interval on 4q21 (ref. 1). Here we study three Chinese families carrying DCI1. We find that the affected individuals of two families also presented with progressive sensorineural high-frequency hearing loss (gene DfNA39). We identified three disease-specific mutations within the dentin sialophosphoprotein gene (DSPP) in these three families. We detected a G-->A transition at the donor-splicing site of intron 3 in one family without DFNA39, a mutation predicted to result in the skipping of exon 3. In two other families affected with both DGI1 and DFNA39, however, we identified two independent nucleotide transversions in exons a and 3 of DSPP, respectively. that cause missense mutations of two adjacent amino-acid residues in the predicted transmembrane region of the protein. Moreover, transcripts of DSPP previously reported to be expressed specifically in teeth(2) are also detected in the inner ear of mice. We have thus demonstrated for the first time that distinct mutations in DSPP are responsible for the clinical manifestations of DGI1 with or without DFNA39.