Isolated brachydactyly type E caused by a HOXD13 nonsense mutation: a case report.
Isolated brachydactyly type E caused by a HOXD13 nonsense mutation: a case report.
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DOI：
10.1186/1471-2350-13-4
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发表时间：
2012-01-10
影响因子：
--
通讯作者：
Latos-Bieleńska A
中科院分区：
文献类型：
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作者：
Jamsheer A;Sowińska A;Kaczmarek L;Latos-Bieleńska A
E 型短指畸形（BDE；MIM#113300）的特点是掌骨、跖骨和指骨缩短，主要影响肢体的轴后射线。 BDE 可能作为一种孤立的特征或作为一种综合征的一部分出现。分离的 BDE 很少见，并且在大多数情况下，其分子发病机制迄今尚未得到解决。最初，分离出的 BDE 的分子原因已在 2 个家族中得到阐明，并被证明是由 HOXD13 基因同源域的杂合错义突变引起的。自最初的手稿以来，仅在表现出分离的 BDE 的单个家族中报告了进一步的 HOXD13 突变。在本文中，我们报告了一个波兰家庭，其表现出由一种新型无义杂合 HOXD13 突变引起的分离 BDE。我们调查了一名波兰女性先证者和她的父亲，他们都受到分离的 BDE 的影响，我们在他们的 HOXD13 基因中发现了无义杂合突变 c.820C > T(p.R274X)。到目前为止，只有两个位于 HOXD13 转录因子同源域内的错义 HOXD13 取代（p.S308C 和 p.I314L）以及一个无义突变（p.E181X）与 BDE 相关。这两种错义变化都被认为会改变蛋白质的 DNA 结合亲和力。在我们的先证者中鉴定出的变异 p.R274X 是第四个 HOXD13 突变，也是第二个截短（无义）突变，据报道会导致典型的分离 BDE。我们将我们的临床和分子发现参考之前描述的 HOXD13 相关表型和突变。
Brachydactyly type E (BDE; MIM#113300) is characterized by shortening of the metacarpal, metatarsal, and often phalangeal bones, and predominantly affects postaxial ray(s) of the limb. BDE may occur as an isolated trait or as part of a syndrome. Isolated BDE is rare and in the majority of cases the molecular pathogenesis has so far not been resolved. Originally, the molecular cause of isolated BDE has been unravelled in 2 families and shown to result from heterozygous missense mutations in the homeodomain of the HOXD13 gene. Since the initial manuscript, one further HOXD13 mutation has been reported only in a single family manifesting isolated BDE. In this paper, we report on a Polish family exhibiting isolated BDE caused by a novel nonsense heterozygous HOXD13 mutation. We investigated a Polish female proband and her father, both affected by isolated BDE, in whom we identified a nonsense heterozygous mutation c.820C > T(p.R274X) in the HOXD13 gene. So far, only two missense HOXD13 substitutions (p.S308C and p.I314L), localized within the homeodomain of the HOXD13 transcription factor, as well as a single nonsense mutation (p.E181X) were associated with BDE. Both missense changes were supposed to alter DNA binding affinity of the protein. The variant p.R274X identified in our proband is the fourth HOXD13 mutation, and the second truncating (nonsense) mutation, reported to result in typical isolated BDE. We refer our clinical and molecular findings to the previously described HOXD13 associated phenotypes and mutations.