Gladwin A J, Dixon J, Loftus S K, Edwards S, Wasmuth J J, Hennekam R C, Dixon M J
School of Biological Sciences, University of Manchester, UK.
Hum Mol Genet. 1996 Oct;5(10):1533-8. doi: 10.1093/hmg/5.10.1533.
Treacher Collins syndrome is an autosomal dominant disorder of craniofacial development the features of which include conductive hearing loss and cleft palate. Recently, the Treacher Collins syndrome gene (TCOF1) has been positionally cloned and a series of five mutations within the coding sequence of the gene identified. In the current investigation, seven exons of TCOF1 have been identified which has permitted the identification of additional mutations in the gene. The mutations that have been identified are three distinct deletions and an insertion, which cause a frameshift, and a missense mutation which inactivates a donor splice site with extension of transcription into the intron. To date, all 10 of the mutations which have been reported result in a premature termination codon and are unique to a given family. As these mutations are spread throughout the gene, these observations provide further support for the hypothesis that Treacher Collins syndrome results from haploinsufficiency, although a dominant negative effect cannot, at this stage, be excluded.
特雷彻·柯林斯综合征是一种常染色体显性颅面发育障碍疾病，其特征包括传导性听力损失和腭裂。最近，已对特雷彻·柯林斯综合征基因（TCOF1）进行了定位克隆，并在该基因的编码序列中鉴定出一系列五个突变。在当前研究中，已鉴定出TCOF1的七个外显子，这使得能够识别该基因中的其他突变。已鉴定出的突变有三个不同的缺失和一个插入，这些导致了移码，还有一个错义突变，该突变使一个供体剪接位点失活，转录延伸到内含子中。迄今为止，已报道的所有10个突变都会导致过早终止密码子，并且特定家族具有独特性。由于这些突变遍布整个基因，这些观察结果进一步支持了以下假设：特雷彻·柯林斯综合征是由单倍体不足引起的，尽管现阶段不能排除显性负效应。
