Iwaizumi Moriya, Taniguchi Terumi, Kojima Risa, Osawa Harumo, Tatsuta Kyota, Sakata Mayu, Osawa Satoshi, Kurachi Kiyotaka, Sugimoto Ken
Department of Laboratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan.
Clinical and Molecular Genetics Center, Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan.
Hered Cancer Clin Pract. 2025 Jan 8;23(1):1. doi: 10.1186/s13053-024-00297-1.
Familial adenomatous polyposis (FAP) is an autosomal dominant colorectal tumour syndrome characterised by the formation of multiple adenomatous polyps throughout the colon. It is important to understand the extracolonic phenotype that characterizes FAP. Most previous case reports of patients with both FAP and intellectual disability (ID) have described deletions in all or part of chromosome 5q, including the APC locus. However, it remains unclear whether the ID phenotype in patients with FAP is due to APC disruption or another genetic defect in the deleted 5q region.
Patient of family 1 is a 32-year-old woman presented with > 500 colorectal adenomatous polyps, gastric fundic gland polyposis, several duodenal adenomas, and mild intellectual disability (ID). She had no known family history of the FAP phenotype or ID. By copy number trio analysis, a 15.4 Mb interstitial heterozygous de novo deletion including APC region was observed in 5q21.2. q22.3. The patient in family 2 was a 29-year-old man with approximately 50 colorectal adenomatous polyps, fundic gland polyposis in the stomach, non-ampullary adenomas in the duodenum, and mild ID. He had no family history of the FAP phenotype or ID. Using copy number trio analysis, a de novo 9.8 Mb heterozygous deletion was identified on 5q22.1. q23.1 which includes the APC region.
Based on previous reports and the present study, we narrowed down the 5p deletion region associated with ID in FAP. Further investigation is required to understand ID due to 5q stromal deletion.
家族性腺瘤性息肉病（FAP）是一种常染色体显性遗传性结直肠肿瘤综合征，其特征是在整个结肠形成多个腺瘤性息肉。了解FAP的结肠外表型很重要。以前大多数关于FAP和智力残疾（ID）患者的病例报告都描述了5号染色体长臂全部或部分区域的缺失，包括腺瘤性息肉病（APC）基因座。然而，FAP患者的ID表型是由于APC破坏还是5号染色体长臂缺失区域中的其他遗传缺陷仍不清楚。
家族1的患者是一名32岁女性，患有超过500个结直肠腺瘤性息肉、胃底腺息肉、多个十二指肠腺瘤以及轻度智力残疾（ID）。她没有已知的FAP表型或ID家族史。通过拷贝数三联体分析，在5q21.2 - q22.3区域观察到一个15.4 Mb的间质性杂合新生缺失，包括APC区域。家族2的患者是一名29岁男性，患有大约50个结直肠腺瘤性息肉、胃底腺息肉、十二指肠非壶腹腺瘤以及轻度ID。他没有FAP表型或ID家族史。使用拷贝数三联体分析，在5q22.1 - q23.1区域鉴定出一个9.8 Mb的新生杂合缺失，其中包括APC区域。
基于之前的报告和本研究，我们缩小了FAP中与ID相关的5号染色体长臂缺失区域。需要进一步研究以了解由于5号染色体长臂间质性缺失导致的ID。
