The Modified Shields Classification and 12 Families with Defined DSPP Mutations.
The Modified Shields Classification and 12 Families with Defined DSPP Mutations.
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作者：
已知牙本质涎磷蛋白（DSPP）的突变会导致牙本质发育不良II型（DD-II）、牙本质发育不良II型（DGI-II）和牙本质发育不良III型（DGI-III），严重程度依次增加。DSPP突变分为两组：影响蛋白质靶向的5′-组和将翻译转移到-1阅读框的3′-组。使用全外显子组序列（WES）分析和单分子实时（SMRT）测序，我们确定了12个家庭的致病DSPP突变。其中三个突变是新的：c.53T>C/p。（Val18Ala）; c.3461delG/p.（Ser1154Metfs*160）;和c.3700delA/p.（Ser1234Alafs*80）。我们建议遗传分析从先证者DNA的WES分析开始，以确定导致成骨缺失显性形式的COL 1A 1和COL 1A 2突变、5′-DSPP突变和DSPP重复区边缘附近的3′-DSPP移码，以及当未确定致病突变时的SMRT测序。在回顾文献并纳入新信息后，显示在具有5 '-Dspp或3'-Dspp突变的敲入小鼠之间观察到的细胞病理学存在明显差异，我们提出了基于病因突变而不是表型严重程度的修改的Shields分类，以便识别出5 '-DSPP缺陷的患者被诊断为DGI-III，而具有3'-DSPP缺陷的患者被诊断为DGI-II。
Mutations in Dentin Sialophosphoprotein (DSPP) are known to cause, in order of increasing severity, dentin dysplasia type-II (DD-II), dentinogenesis imperfecta type-II (DGI-II), and dentinogenesis imperfecta type-III (DGI-III). DSPP mutations fall into two groups: a 5′-group that affects protein targeting and a 3′-group that shifts translation into the −1 reading frame. Using whole-exome sequence (WES) analyses and Single Molecule Real-Time (SMRT) sequencing, we identified disease-causing DSPP mutations in 12 families. Three of the mutations are novel: c.53T>C/p.(Val18Ala); c.3461delG/p.(Ser1154Metfs*160); and c.3700delA/p.(Ser1234Alafs*80). We propose genetic analysis start with WES analysis of proband DNA to identify mutations in COL1A1 and COL1A2 causing dominant forms of osteogenesis imperfecta, 5′-DSPP mutations, and 3′-DSPP frameshifts near the margins of the DSPP repeat region, and SMRT sequencing when the disease-causing mutation is not identified. After reviewing the literature and incorporating new information showing distinct differences in the cell pathology observed between knockin mice with 5′-Dspp or 3′-Dspp mutations, we propose a modified Shields Classification based upon the causative mutation rather than phenotypic severity such that patients identified with 5′-DSPP defects be diagnosed as DGI-III, while those with 3′-DSPP defects be diagnosed as DGI-II.
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影响因子：
3.7
作者：
Andersson K;Dahllöf G;Lindahl K;Kindmark A;Grigelioniene G;Åström E;Malmgren B
通讯作者：
Malmgren B
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
--
作者：
Bai H;Agula H;Wu Q;Zhou W;Sun Y;Qi Y;Latu S;Chen Y;Mutu J;Qiu C
通讯作者：
Qiu C
影响因子：
3
作者：
Habelitz, S;Balooch, M;Marshall, GW
通讯作者：
Marshall, GW
影响因子：
1.9
作者：
Kida, Miyuki;Tsutsumi, Tomonori;Ariga, Tadashi
通讯作者：
Ariga, Tadashi