Eccles D M, van der Luijt R, Breukel C, Bullman H, Bunyan D, Fisher A, Barber J, du Boulay C, Primrose J, Burn J, Fodde R
Wessex Clinical Genetics Service, Southampton University Hospital Trust.
Am J Hum Genet. 1996 Dec;59(6):1193-201.
Desmoid tumors are slowly growing fibrous tumors highly resistant to therapy and often fatal. Here, we report hereditary desmoid disease (HDD), a novel autosomal dominant trait with 100% penetrance affecting a three-generation kindred. Desmoid tumors are usually a complication of familial adenomatous polyposis, a predisposition to the early development of premalignant adenomatous polyps in the colorectum due to chain-terminating mutations of the APC gene. In general, one or more members in approximately 10% of the FAP families manifest desmoid tumors. Affected individuals from the HDD kindred are characterized by multifocal fibromatosis of the paraspinal muscles, breast, occiput, arms, lower ribs, abdominal wall, and mesentery. Osteomas, epidermal cysts, and other congenital features were also observed. We show that HDD segregates with an unusual germ-line chain-terminating mutation at the 3' end of the APC gene (codon 1924) with somatic loss of the wild-type allele leading to tumor development.
硬纤维瘤是生长缓慢的纤维性肿瘤，对治疗高度耐药，且往往致命。在此，我们报告遗传性硬纤维瘤病（HDD），这是一种新型常染色体显性性状，具有100%的外显率，影响一个三代家族。硬纤维瘤通常是家族性腺瘤性息肉病的并发症，由于APC基因的链终止突变，易导致结直肠中癌前腺瘤性息肉的早期发生。一般来说，约10%的家族性腺瘤性息肉病（FAP）家族中有一个或多个成员会出现硬纤维瘤。来自HDD家族的受影响个体的特征是椎旁肌、乳房、枕部、手臂、下肋骨、腹壁和肠系膜的多灶性纤维瘤病。还观察到骨瘤、表皮囊肿和其他先天性特征。我们发现，HDD与APC基因3'端（密码子1924）的一种不寻常的种系链终止突变相关联，野生型等位基因的体细胞缺失导致肿瘤发生。
