Young J, Simms L A, Tarish J, Buttenshaw R, Knight N, Anderson G J, Bell A, Leggett B
Glaxo Conjoint Gastroenterology Laboratory, Royal Brisbane Hospital Foundation Clinical Research Centre, Australia.
Hum Mutat. 1998;11(6):450-5. doi: 10.1002/(SICI)1098-1004(1998)11:6<450::AID-HUMU5>3.0.CO;2-P.
A family is presented with attenuated familial adenomatous polyposis of variable phenotype. The clinical features range from sparse right-sided polyposis and cancer in the proximal colon at the age of 34 to pan-colonic polyposis and cancer at the age of 68. Rectal sparing is common to all affected members. Heteroduplex analysis detected bands of altered mobility in exon 9 of the APC gene in all affected family members. Subsequently, a frameshift mutation was found in the alternatively spliced region of exon 9 at codon 398 which resulted in a stop signal 4 codons downstream. Alternatively spliced transcripts that delete the mutation were readily amplified from normal colonic mucosa and therefore create a mechanism for the attenuated phenotype seen in this family.
本文报道了一个具有可变表型的轻度家族性腺瘤性息肉病家族。临床特征从34岁时近端结肠右侧稀疏息肉病和癌症到68岁时全结肠息肉病和癌症不等。所有受影响成员均常见直肠 spared。异源双链分析在所有受影响家族成员的APC基因外显子9中检测到迁移率改变的条带。随后，在密码子398的外显子9可变剪接区域发现了一个移码突变，该突变在下游4个密码子处产生了一个终止信号。从正常结肠黏膜中很容易扩增出缺失该突变的可变剪接转录本，因此为该家族中观察到的轻度表型创造了一种机制。
