Tanabe Hiroki, Koshizuka Yasuyuki, Tanaka Kazuyuki, Takahashi Kenji, Ijiri Masami, Takahashi Keitaro, Ando Katsuyoshi, Ueno Nobuhiro, Kashima Shin, Sarashina Takeo, Moriichi Kentaro, Mitsube Kenrokuro, Mizukami Yusuke, Fujiya Mikihiro, Makita Yoshio
Oncology Center, Asahikawa Medical University Hospital, Asahikawa, Japan.
Genetic Oncology Department, Asahikawa Medical University Hospital, Asahikawa, Japan.
Hum Genome Var. 2024 Dec 4;11(1):46. doi: 10.1038/s41439-024-00301-z.
Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by germline variants in the APC gene, leading to the development of numerous colorectal polyps and significantly increases the risk of colorectal cancer. A diagnosis is typically made using colonoscopy, and genetic testing can assist in patient surveillance and carrier identification. Recent advances include the use of whole-genome array comparative genomic hybridization (a-CGH), which provides better resolution of genetic imbalances. We aimed to explore the specific features of FAP patients with whole APC gene deletions using high-resolution a-CGH and to compare patient characteristics. Two polyposis patients with whole APC deletions were identified, and the lost genetic sizes ranged from 0.3-1.1 Mb. Nervous abnormalities were a characteristic symptom in a patient with a 1.1 Mb loss. A patient with an approximately 0.3 Mb loss, which included the entire APC gene, presented a polyposis phenotype without intellectual disability. The comparison of genetic losses, with or without intellectual disability, revealed 7 genetic changes. Consequently, EPB41L4A is a candidate gene associated with the neurogenic phenotype.
家族性腺瘤性息肉病（FAP）是一种常染色体显性综合征，由APC基因的种系变异引起，导致大量结肠息肉的发生，并显著增加患结直肠癌的风险。诊断通常通过结肠镜检查进行，基因检测有助于患者监测和携带者识别。最近的进展包括使用全基因组阵列比较基因组杂交（a-CGH），它能更好地解析基因失衡。我们旨在利用高分辨率a-CGH探索全APC基因缺失的FAP患者的特定特征，并比较患者特征。识别出两名全APC基因缺失的息肉病患者，基因缺失大小范围为0.3 - 1.1 Mb。一名基因缺失1.1 Mb的患者出现神经异常这一特征性症状。一名基因缺失约0.3 Mb（包括整个APC基因）的患者表现出息肉病表型但无智力残疾。对有或无智力残疾的基因缺失情况进行比较，发现了7种基因变化。因此，EPB41L4A是与神经源性表型相关的候选基因。
