Introduction

Familial adenomatous polyposis (FAP) is an autosomal dominant-inherited disease caused by germline variants in the APC gene. It is characterized by the development of hundreds to thousands of adenomatous polyps in colon and rectum. Recently, biallelic germline variants in the base excision repair (BER) gene: MUTYH have been identified in patients with attenuated FAP and/or negative APC result. It can be responsible for an autosomal recessive inherited colorectal cancer syndrome (MAP syndrome: MUTYH-associated polyposis).

Objective

The aim of this study was to evaluate germline variants of MUTYH gene in Tunisian patients with attenuated FAP.

Methods

thirteen unrelated patients from Tunisia with attenuated FAP were screened for MUTYH germline variants. Direct sequencing was performed to identify point variants in this gene.

Results

A Biallelic MUTYH germline variant were found in all patients and showed an attenuated polyposis phenotype almost of them without extra-colic manifestations:

The known pathogenic frameshift variant c.1227_1228dupGG (p. Glu410Glyfs) was found, in homozygous state, in 13 index patients.

Conclusion

Patients with attenuated familial adenomatous polyposis (<=100) and no obvious vertical transmission of the disease should be considered for MUTYH gene testing.

中文翻译：

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c.1227_1228dupGG（p.Glu410Glyfs），这是突尼斯人患有MUTYH相关性息肉病的常见变体。

介绍

家族性腺瘤性息肉病（FAP）是由APC基因种系变异引起的常染色体显性遗传病。它的特征是在结肠和直肠中形成数百至数千个腺瘤性息肉。最近，已在FAP减低和/或APC阴性的患者中发现了碱基切除修复（BER）基因：MUTYH中的双等位基因种系变体。它可能导致常染色体隐性遗传性大肠癌综合征（MAP综合征：MUTYH相关性息肉病）。

目的

这项研究的目的是评估突尼斯FAP减毒患者MUTYH基因的种系变异。

方法

筛选了来自突尼斯的13例FAP减毒的无关患者的MUTYH种系变异。进行直接测序以鉴定该基因中的点变体。

结果

在所有患者中均发现了双等位基因MUTYH生殖系变体，并表现出息肉病减毒表型，几乎所有患者均无结肠外表现：

在纯合子状态下，在13名索引患者中发现了已知的致病性移码变体c.1227_1228dupGG（p。Glu410Glyfs）。

结论

MUTYH基因检测应考虑家族性腺瘤性息肉病（<= 100）减毒且该病无明显垂直传播的患者。