Fujioka Hirotaka, Ariga Tadashi, Horiuchi Katsumi, Ishikiriyama Satoshi, Oyama Kimie, Otsu Makoto, Kawashima Kunihiro, Yamamoto Yuhei, Sugihara Tsuneki, Sakiyama Yukio
Research Group of Human Gene Therapy, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
Pediatr Int. 2008 Dec;50(6):806-9. doi: 10.1111/j.1442-200X.2008.02650.x.
Treacher Collins syndrome (TCS) is a disorder of craniofacial development, that is caused by mutations in the TCOF1 gene. TCS is inherited as an autosomal dominant trait, and haploinsufficiency of the TCOF1 gene product treacle is proposed to be etiologically involved.
Mutational analysis of the TCOF1 gene was done in 10 patients diagnosed with TCS using single-strand conformation polymorphism and direct sequencing.
Among these 10 patients, a novel 9 bp deletion was found, together with a previously reported 2 bp deletion, a novel missense mutation and a novel nonsense mutation in three different families. Familial studies allowed judgment of whether these abnormal findings were responsible for the TCS phenotype, or not. The 9 bp deletion of three amino acids Lys-Glu-Lys (1378-1380), which was located in the nuclear localization domain of treacle, seemed not essential for the treacle function. In contrast, the novel mutation of Ala26Val is considered to affect the LisH domain, an important domain of treacle. All of the mutations thus far detected in exon 5 have resulted in frameshift, but a nonsense mutation was detected (Lys159Stop).
The information obtained in the present study provides additional insights into the functional domains of treacle.
特雷彻·柯林斯综合征（TCS）是一种颅面发育障碍疾病，由TCOF1基因突变引起。TCS以常染色体显性性状遗传，据推测TCOF1基因产物treacle的单倍剂量不足与病因有关。
采用单链构象多态性和直接测序法，对10例诊断为TCS的患者进行TCOF1基因突变分析。
在这10例患者中，发现了一个新的9bp缺失，以及之前报道的一个2bp缺失、一个新的错义突变和三个不同家族中的一个新的无义突变。家族研究有助于判断这些异常发现是否导致了TCS表型。位于treacle核定位域的9bp缺失导致三个氨基酸赖氨酸-谷氨酸-赖氨酸（1378-1380）缺失，这似乎对treacle功能并非至关重要。相比之下，新的Ala26Val突变被认为会影响treacle一个重要的结构域——LisH结构域。迄今为止，在第5外显子中检测到的所有突变均导致移码，但检测到一个无义突变（Lys159Stop）。
本研究获得的信息为treacle的功能结构域提供了更多见解。
