Identification of a Novel Pathogenic Rearrangement Variant of the APC Gene Associated with a Variable Spectrum of Familial Cancer.
Identification of a Novel Pathogenic Rearrangement Variant of the APC Gene Associated with a Variable Spectrum of Familial Cancer.
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DOI：
10.3390/diagnostics11030411
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发表时间：
2021-02-28
期刊：
影响因子：
--
通讯作者：
Pérez-Ibave DC
中科院分区：
文献类型：
--
作者：
Garza-Rodríguez ML;Treviño V;Pérez-Maya AA;Rodríguez-Gutiérrez HF;González-Escamilla M;Elizondo-Riojas MÁ;Ramírez-Correa GA;Vidal-Gutiérrez O;Burciaga-Flores CH;Pérez-Ibave DC
家族性腺瘤性息肉病（FAP）是一种常染色体显性遗传病，其特征是存在多个结直肠腺瘤，由腺瘤性息肉病结肠基因（APC）的种系变异引起。已经确定了300多种种系变异。检测新的变异对于理解病理生理学机制非常重要。我们在一名先证者患者中使用新一代测序（NGS）技术鉴定出一种新的致病性种系变异。该变异是一种复杂的重排（c.422 + 1123_532 - 577 del ins 423 - 1933_423 - 1687 inv），导致APC基因的第5外显子完全缺失。为了研究其他家庭成员中的变异，我们设计了一种终点PCR方法，随后进行桑格测序。该变异在先证者患者的母亲、一个女儿、她的兄弟、两个表亲、一个侄女和第二个侄子中被发现。在发现变异的患者中，我们发现了非典型的临床症状，包括下颌癌、卵巢癌、乳腺癌、胰腺癌和胃癌。为这个家庭提供了遗传咨询和癌症预防策略。根据美国医学遗传学学会（ACMG）的指南，这种新的变异被认为是PVS1变异（致病性的极强证据），并且结合临床数据，它可用于早期监测和适当的治疗。
Familial adenomatous polyposis (FAP) is an autosomal-dominant condition characterized by the presence of multiple colorectal adenomas, caused by germline variants in the adenomatous polyposis coli (APC) gene. More than 300 germline variants have been characterized. The detection of novel variants is important to understand the mechanisms of pathophysiology. We identified a novel pathogenic germline variant using next-generation sequencing (NGS) in a proband patient. The variant is a complex rearrangement (c.422+1123_532-577 del ins 423-1933_423-1687 inv) that generates a complete deletion of exon 5 of the APC gene. To study the variant in other family members, we designed an endpoint PCR method followed by Sanger sequencing. The variant was identified in the proband patient’s mother, one daughter, her brother, two cousins, a niece, and a second nephew. In patients where the variant was identified, we found atypical clinical symptoms, including mandibular, ovarian, breast, pancreatic, and gastric cancer. Genetic counseling and cancer prevention strategies were provided for the family. According to the American College of Medical Genetics (ACMG) guidelines, this novel variant is considered a PVS1 variant (very strong evidence of pathogenicity), and it can be useful in association with clinical data for early surveillance and suitable treatment.
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影响因子：
2
作者：
Schirosi, Laura;Pellegrino, Marcello;Greco, Marilena
通讯作者：
Greco, Marilena
影响因子：
4
作者：
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影响因子：
3.9
作者：
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影响因子：
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作者：
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通讯作者：
Hegde, Madhuri
DOI：
10.1016/j.mrfmmm.2009.09.004
发表时间：
2010-11-10
影响因子：
2.3
作者：
Heinen, Christopher D.
通讯作者：
Heinen, Christopher D.