Molecular analysis of SALL1 mutations in Townes-Brocks syndrome
Molecular analysis of SALL1 mutations in Townes-Brocks syndrome
复制标题
DOI：
10.1086/302238
复制
发表时间：
1999-02-01
影响因子：
9.8
通讯作者：
Engel, W
中科院分区：
文献类型：
--
作者：
Kohlhase, J;Taschner, PEM;Engel, W
Townes-Brocks综合征（TBS）是一种常染色体显性遗传畸形综合征，以肛门、肾肢和耳畸形为特征。最近，我们发现，在假定的锌指转录因子基因SALL 1突变导致TBS。为了确定SALL 1突变谱并研究TBS的基因型-表型相关性，我们检查了另外23个具有TBS或类似表型的SALL 1突变家族。在这些家庭中的9个突变被确定。以前没有描述过突变。这些突变中有两个是无义突变，其中一个发生在三个不相关的家族中。其中5个突变是短缺失。所有的突变都位于第一个双锌指（DZF）编码区的5'，因此预测会导致推定的过早终止的蛋白质缺乏所有DZF结构域。这表明只有去除DZF结构域的SALL 1突变才导致TBS。我们还提供了证据表明，在罕见的情况下，SALL 1突变可导致类似于Goldenhar综合征的表型。然而，TBS的表型差异似乎并不取决于突变位点。
Townes-Brocks syndrome (TBS) is an autosomal dominantly inherited malformation syndrome characterized by anal, renal limb, and ear anomalies. Recently, we showed that mutations in the putative zinc finger transcription factor gene SALL1 cause TBS. To determine the spectrum of SALL1 mutations and to investigate the genotype-phenotype correlations in TBS, we examined 23 additional families with TBS or similar phenotypes for SALL1 mutations. In 9 of these families mutations were identified. None of the mutations has previously been described. Two of these mutations are nonsense mutations, one of which occurred in three unrelated families. Five of the mutations are short deletions. All of the mutations are located 5' of the first double zinc finger (DZF) encoding region and are therefore predicted to result in putative prematurely terminated proteins lacking all DZF domains. This suggests that only SALL1 mutations that remove the DZF domains result in TBS. We also present evidence that in rare cases SALL1 mutations can lead to phenotypes similar to Goldenhar syndrome. However, phenotypic differences in TBS do not seem to depend on the site of mutation.