Identification of 5 novel germline APC mutations and characterization of clinical phenotypes in Japanese patients with classical and attenuated familial adenomatous polyposis

被引：13

作者：

Tao H. ^{[1
]}

Shinmura K. ^{[1
]}

Yamada H. ^{[1
]}

Maekawa M. ^{[2
]}

Osawa S. ^{[3
]}

Takayanagi Y. ^{[3
]}

Okamoto K. ^{[4
]}

Terai T. ^{[3
]}

Mori H. ^{[1
]}

Nakamura T. ^{[5
]}

Sugimura H. ^{[1
]}

机构：

[1] First Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, 1-20-1 Handayama, Higashi Ward

[2] Department of Laboratory Medicine, Hamamatsu University, School of Medicine, Hamamatsu, Shizuoka 431-3192, 1-20-1 Handayama, Higashi Ward

[3] First Department of Medicine, Hamamatsu University, School of Medicine, Hamamatsu, Shizuoka 431-3192, 1-20-1 Handayama, Higashi Ward

[4] Department of Surgery, Fujinomiya City General Hospital, 3-1 Nishiki-cho, Fujinomiya

[5] Second Department of Surgery, Hamamatsu University, School of Medicine, Hamamatsu, Shizuoka 431-3192, 1-20-1 Handayama, Higashi Ward

来源：

BMC Research Notes | / 3卷 / 1期

基金：

日本学术振兴会;

关键词：

Familial Adenomatous Polyposis; Adenomatous Polyposis Coli; Desmoid Tumor; Familial Adenomatous Polyposis Patient; Adenomatous Polyposis Coli Gene;

D O I：

10.1186/1756-0500-3-305

中图分类号：

学科分类号：

摘要：

Background: Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary disease characterized by multiple colorectal adenomatous polyps and frequent extracolonic manifestations. An attenuated form of FAP (AFAP) is diagnosed based on a milder colorectal phenotype, and the colorectal phenotype of (A)FAP has been linked to germline APC mutations. The relationships between the spectrum of mutations and extracolonic manifestations are quite well known, but they need to be further defined. Findings. Nine germline APC mutations, but no large deletions, were identified in the APC locus of 8 (A)FAP patients, and 5 of the mutations, c.446A > T (p.Asp149Val), c.448A > T (p.Lys150X), c.454-457insAGAA (p.Glu152ArgfsX17), c.497insA (p.Thr166AsnfsX2), and c.1958G > C (p.Arg653Ser), were novel mutations. In one patient the p.Asp149Val mutation and p.Lys150X mutation were detected in the same APC allele. The c.1958G > C mutation was located in the last nucleotide of exon 14, and RT-PCR analysis revealed that the mutation resulted in abnormal splicing. The above findings meant that a nonsense mutation, a frameshift mutation, or an exonic mutation leading to abnormal splicing was found in every patient. The following phenotypes, especially extracolonic manifestations, were observed in our (A)FAP patients: (1) multiple gastroduodenal adenomas and early-onset gastric carcinoma in AFAP patients with an exon 4 mutation; (2) a desmoid tumor in two FAP patients with a germline APC mutation outside the region between codons 1403 and 1578, which was previously reported to be associated with the development of desmoid tumors in FAP patients; (3) multiple myeloma in an AFAP patient with an exon 4 mutation. Conclusions. Nine germline APC mutations, 5 of them were novel, were identified in 8 Japanese (A)FAP patients, and some associations between germline APC mutations and extracolonic manifestations were demonstrated. These findings should contribute to establishing relationships between germline APC mutations and the extracolonic manifestations of (A)FAP patients in the future. © 2010 Sugimura et al; licensee BioMed Central Ltd.

引用

共 37 条

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