一个新的 DSPP 突变导致一个大型蒙古家族的 II 型牙本质生成不全。

A novel DSPP mutation causes dentinogenesis imperfecta type II in a large Mongolian family.

机构信息

Inner Mongolia University, Huhhot, China.

出版信息

BMC Med Genet. 2010 Feb 10;11:23. doi: 10.1186/1471-2350-11-23.

DOI:10.1186/1471-2350-11-23

PMID:20146806

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2829541/

Abstract

BACKGROUND

Several studies have shown that the clinical phenotypes of dentinogenesis imperfecta type II (DGI-II) may be caused by mutations in dentin sialophosphoprotein (DSPP). However, no previous studies have documented the clinical phenotype and genetic basis of DGI-II in a Mongolian family from China.

METHODS

We identified a large five-generation Mongolian family from China with DGI-II, comprising 64 living family members of whom 22 were affected. Linkage analysis of five polymorphic markers flanking DSPP gene was used to genotype the families and to construct the haplotypes of these families. All five DSPP exons including the intron-exon boundaries were PCR-amplified and sequenced in 48 members of this large family.

RESULTS

All affected individuals showed discoloration and severe attrition of their teeth, with obliterated pulp chambers and without progressive high frequency hearing loss or skeletal abnormalities. No recombination was found at five polymorphic markers flanking DSPP in the family. Direct DNA sequencing identified a novel A-->G transition mutation adjacent to the donor splicing site within intron 3 in all affected individuals but not in the unaffected family members and 50 unrelated Mongolian individuals.

CONCLUSION

This study identified a novel mutation (IVS3+3A-->G) in DSPP, which caused DGI-II in a large Mongolian family. This expands the spectrum of mutations leading to DGI-II.

摘要

背景

多项研究表明，牙本质生成不全 II 型（DGI-II）的临床表型可能是由牙本质涎磷蛋白（DSPP）基因突变引起的。然而，以前没有研究记录过来自中国蒙古族的 DGI-II 的临床表型和遗传基础。

方法

我们在中国鉴定了一个大型的五世代蒙古族 DGI-II 家系，共 64 名在世的家族成员，其中 22 名受影响。使用侧翼 DSPP 基因的五个多态性标记的连锁分析对家系进行基因分型，并构建这些家系的单体型。在这个大家庭的 48 名成员中，我们对所有五个 DSPP 外显子进行了 PCR 扩增和测序，包括内含子-外显子边界。

结果

所有受影响的个体均表现出牙齿变色和严重磨损，牙髓腔闭塞，无进行性高频听力损失或骨骼异常。在该家族的五个侧翼 DSPP 多态性标记中未发现重组。直接 DNA 测序在所有受影响的个体中均发现了一个新的 A-->G 转换突变，位于内含子 3 的供体位点附近，但在未受影响的家族成员和 50 名无关的蒙古族个体中未发现。