Long-term follow-up and novel splice donor mutation in MEN1 in a Chinese family.
Long-term follow-up and novel splice donor mutation in MEN1 in a Chinese family.
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中国家庭 MEN1 的长期随访和新型剪接供体突变
DOI：
10.18632/oncotarget.23100
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发表时间：
2018-01-05
期刊：
影响因子：
--
通讯作者：
Zhu F
中科院分区：
文献类型：
--
作者：
Li M;Liu Q;Liu P;Yi X;Guan X;Yu A;Liu L;Zhu F
MEN 1肿瘤抑制基因的杂合生殖系突变是多发性内分泌腺瘤1型的原因采用全外显子组和桑格测序法分析了两名中国汉族MEN 1家系患者的甲状旁腺和胸部神经内分泌肿瘤标本和DNA。先证者（II-3）在6年的随访中依次被诊断为垂体腺瘤、胰腺肿瘤、肾上腺皮质肿瘤、腹部脂肪瘤和甲状旁腺腺瘤。先证者（III-6）的儿子在此期间也被诊断为胸部神经内分泌肿瘤和甲状旁腺腺瘤。通过RT-PCR和测序研究剪接改变。使用生物信息学评估突变影响。序列分析揭示了一种新的剪接供体突变，MEN 1 IVS 9 + 1G > C，它改变了MEN 1的剪接模式，在menin蛋白的两个核定位信号之前停止翻译。在II-3的甲状旁腺腺瘤和III-6的胸神经内分泌肿瘤中分别鉴定了新的体细胞突变MEN 1 c.1402_1405delGAGG和c.286 C > T，表明MEN 1综合征的两次发病病因。我们的研究揭示了MEN 1的临床和遗传基础，并提供了MEN 1的机制，诊断和管理的见解。
Heterozygous germline mutation of the MEN1 tumor suppressor gene is responsible for multiple endocrine neoplasia type 1. Parathyroid and thoracic neuroendocrine tumor specimens and DNA from two Han Chinese MEN1 family patients were analyzed using whole exome and Sanger sequencing. The proband (II-3) was sequentially diagnosed with pituitary adenoma, pancreatic tumor, adrenal cortical tumor, abdominal lipoma, and parathyroid adenoma during the 6-year follow-up. The son of the proband (III-6) was also diagnosed with a thoracic neuroendocrine tumor and a parathyroid adenoma during this period. Splice alterations were studied by RT-PCR and sequencing. The mutation impact was evaluated using bioinformatics. Sequence analysis revealed a novel splice donor mutation, MEN1 IVS9 + 1G > C, that changed the splicing mode of MEN1 to halt translation before two nuclear localization signals in the menin protein. Novel somatic mutations, MEN1 c.1402_1405delGAGG and c.286 C > T, were identified in the parathyroid adenoma of II-3 and thoracic neuroendocrine tumor of III-6, respectively, indicating a two-hit etiology of MEN1 syndrome. Our study revealed the clinical and genetic basis of MEN1 in this Han Chinese family and provides insight into MEN1 mechanisms, diagnosis, and management.
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DOI：
10.1073/pnas.95.4.1630
发表时间：
1998-02-17
影响因子：
11.1
作者：
Guru, SC;Goldsmith, PK;Chandrasekharappa, SC
通讯作者：
Chandrasekharappa, SC
影响因子：
5.8
作者：
Carrasco, CA;González, AA;Fardella, CE
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影响因子：
3.4
作者：
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DOI：
10.1093/bioinformatics/btv009
发表时间：
2015-05-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Shihab HA;Rogers MF;Gough J;Mort M;Cooper DN;Day IN;Gaunt TR;Campbell C
通讯作者：
Campbell C
影响因子：
4
作者：
Raghavan, Rani;Shah, Sudeep;Ashavaid, Tester F.
通讯作者：
Ashavaid, Tester F.