Marsh A, Wicking C, Wainwright B, Chenevix-Trench G
Queensland Institute of Medical Research, Brisbane, Australia.
Hum Mutat. 2005 Sep;26(3):283. doi: 10.1002/humu.9365.
Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is an autosomal dominant disorder characterised by multiple basal cell carcinomas, palmar and plantar pitting, odontogenic keratocysts of the jaws and bilamellar calcification of the falx. Mutations in the PTCH gene are responsible for NBCCS but most studies have found mutations in less than half of the cases tested. We used denaturing high performance liquid chromatography (DHPLC) to screen for PTCH mutations in 28 NBCCS cases, most of whom had been previously evaluated by single stranded conformation polymorphism analysis but found to be negative. Protein truncating (n = 10) and missense or indel (n = 4) mutations were found in 14/28 (50%) cases and one additional case carried an unclassified variant, c.2777G>C. Thirteen of the variants were novel. The mutation frequency was similar in inherited and de novo cases. Three of the missense and indel mutations were in the sterol-sensing domain, and one was in the sixth transmembrane domain.
痣样基底细胞癌综合征（NBCCS）是一种常染色体显性疾病，其特征为多发性基底细胞癌、掌跖点状凹陷、颌骨牙源性角化囊肿以及大脑镰双层钙化。PTCH基因突变是NBCCS的病因，但大多数研究发现，在检测的病例中，突变病例不到一半。我们使用变性高效液相色谱法（DHPLC）对28例NBCCS病例进行PTCH突变筛查，其中大多数病例先前已通过单链构象多态性分析进行评估，但结果为阴性。在14/28（50%）的病例中发现了蛋白质截短突变（n = 10）和错义或插入缺失突变（n = 4），另外1例携带未分类变异c.2777G>C。其中13种变异是新发现的。遗传病例和新发病例的突变频率相似。3种错义突变和插入缺失突变位于固醇感应结构域，1种位于第六跨膜结构域。
