A novel pathogenic single nucleotide germline deletion in APC gene in a four generation Chinese family with familial adenomatous polyposis.
A novel pathogenic single nucleotide germline deletion in APC gene in a four generation Chinese family with familial adenomatous polyposis.
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中国四代家族性腺瘤性息肉病家族 APC 基因中新的致病性单核苷酸种系缺失
DOI：
10.1038/s41598-017-10395-x
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发表时间：
2017-09-27
影响因子：
4.6
通讯作者：
Banerjee S
中科院分区：
文献类型：
--
作者：
Zhang Z;Liang S;Wang D;Liang S;Li Y;Wang B;Jiang T;Zhao G;Zhang X;Banerjee S
家族性腺瘤性息肉病（FAP）是一种常染色体显性遗传的癌前病变，与APC基因的种系突变有关。临床上，FAP的特征在于发展为多发性结直肠腺瘤或息肉，如果没有进行手术干预，最终在患者40岁时导致结直肠癌。在这项研究中，我们提出了一个四代中国家庭FAP的临床分子研究。FAP的诊断是根据临床表现，家族史和医疗记录（结肠镜检查和组织病理学）。先证者和所有受影响的家庭成员的遗传筛查进行了有针对性的下一代测序和确证性桑格测序。靶向下一代测序鉴定了APC基因外显子18的一个种系新的杂合单核苷酸缺失[c.3418delC; p.Pro1140Leufs*25]，该缺失与先证者和所有受累家族成员的FAP表型分离，而在未受累家族成员以及相同种族的正常健康对照中不存在。本研究扩大了APC基因的突变谱，为进一步了解APC基因在FAP中的功能提供了依据。
Familial adenomatous polyposis (FAP) is an autosomal dominant precancerous condition which is associated with germline mutations of the APC gene. Clinically, FAP is characterized by the development of multiple colorectal adenomas or polyps which finally result in colorectal cancer by the 40 years age of the patient, if no surgical interventions have been undertaken. In this study, we present a clinical molecular study of a four generation Chinese family with FAP. Diagnosis of FAP was made on the basis of clinical manifestations, family history and medical (colonoscopy and histopathology) records. Genetic screening of the proband and all affected family members were performed by targeted next-generation sequencing and confirmatory Sanger sequencing. Targeted next generation sequencing identified a germline novel heterozygous single nucleotide deletion [c.3418delC; p.Pro1140Leufs*25] in exon18 of APC gene, which segregated with the FAP phenotypes in the proband and in all the affected family members whereas absent in unaffected family members as well as in normal healthy controls of same ethnic origin. Our present study expands the mutational spectrum of APC gene and provides evidence to understand the function of APC gene in FAP.
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影响因子：
3.3
作者：
Ekman M;Mu Y;Lee SY;Edlund S;Kozakai T;Thakur N;Tran H;Qian J;Groeden J;Heldin CH;Landström M
通讯作者：
Landström M
影响因子：
64.5
作者：
GRODEN, J;THLIVERIS, A;WHITE, R
通讯作者：
WHITE, R
影响因子：
3.8
作者：
Odenwald MA;Prosperi JR;Goss KH
通讯作者：
Goss KH
影响因子：
--
作者：
Jiang SS;Li JJ;Li Y;He LJ;Wang QJ;Weng DS;Pan K;Liu Q;Zhao JJ;Pan QZ;Zhang XF;Tang Y;Chen CL;Zhang HX;Xu GL;Zeng YX;Xia JC
通讯作者：
Xia JC
影响因子：
5.2
作者：
Cao, X;Eu, KW;Cheah, PY
通讯作者：
Cheah, PY