High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis
High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis
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DOI：
10.1053/j.gastro.2004.02.022
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发表时间：
2004-06-01
期刊：
影响因子：
29.4
通讯作者：
Ranzani, GN
中科院分区：
文献类型：
--
作者：
Venesio, T;Molatore, S;Ranzani, GN
背景与目的：遗传性大肠息肉病与APC抑癌基因的结构性突变有关。最近，碱基切除修复基因MYH的种系突变与一种隐性遗传形式的疾病有关。本研究的目的是评估意大利减少性家族性腺瘤性息肉病患者MYH和APC易感基因的种系突变频率。方法：采用APC蛋白截断试验和MYH基因组DNA测序方法对14例无血缘关系的患者进行分析。结果：总体而言，我们确定了14个突变携带者中的7个(50%)。2例为APC截短突变杂合子(2/14)，5例为MYH基因突变纯合子或复合杂合子(5/14[36%])。两个MYH错义突变，Y165C和G382D，已经在北欧患者中频繁出现，在我们的调查中也占主导地位。APC相关综合征患者有显性家族性息肉病史，而MYH相关疾病患者要么是明显的散发病例，要么有符合隐性遗传的家族史。在至少30个腺瘤和无垂直传播息肉病家族史的患者中，MYH双等位基因突变携带者高达60%(5/8)。结论：根据我们的数据，有30个腺瘤且无明显垂直传播的家族性腺瘤性息肉病患者应考虑进行MYH基因检测。
Background & Aims: Inherited colorectal polyposis has been linked to constitutive mutations of the APC tumor suppressor gene. Recently, germline mutations in the base excision repair gene MYH have been associated with a recessively inherited form of the disease. The aim of this study was to evaluate germline mutation frequencies of both MYH and APC susceptibility genes in Italian patients with attenuated familial adenomatous polyposis. Methods: The analysis was performed in 14 unrelated patients by using the protein truncation test for APC and genomic DNA sequencing for MYH. Results: Overall, we identified 7 of 14 (50%) mutation carriers. Two patients were heterozygotes for an APC truncating mutation (2 of 14 [14%]), whereas 5 proved to be homozygotes or compound heterozygotes for MYH gene alterations (5 of 14 [36%]). Two MYH missense mutations, Y165C and G382D, already found to be frequent among patients from northern Europe, were also preponderant in our survey. Individuals with APC-associated syndrome showed a dominant family history of polyposis, whereas patients with MYH-associated disease were either apparently sporadic cases or had a family history consistent with recessive inheritance. MYH biallelic mutation carriers were up to 60% (5 of 8) among patients showing at least 30 adenomas and a family history with no vertical transmission of polyposis. Conclusions: On the basis of our data, patients with attenuated familial adenomatous polyposis with >30 adenomas and no obvious vertical transmission of the disease should be considered for MYH gene testing.