A Novel IVS2-1G>A mutation causes aberrant splicing of the HRPT2 gene in a family with hyperparathyroidism-jaw tumor syndrome.
A Novel IVS2-1G>A mutation causes aberrant splicing of the HRPT2 gene in a family with hyperparathyroidism-jaw tumor syndrome.
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一种新型 IVS2-1G>A 突变导致甲状旁腺功能亢进-颌肿瘤综合征家族的 HRPT2 基因剪接异常。
DOI：
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发表时间：
2005
影响因子：
5.8
通讯作者：
B. Cha
中科院分区：
文献类型：
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作者：
S. Moon;Jae‐Hyun Park;Eunmin Kim;Ju‐Hee Kim;J. Han;S. Yoo;K. Yoon;M. Kang;K. Lee;H. Son;S. Kang;Se;Kyung Kim;S. Yoon;Jae‐Gahb Park;Il;H. Kang;S. Hong;Kyung Kim;B. Cha
HRPT2 是与甲状旁腺功能亢进症下颌肿瘤 (HPT-JT) 综合征相关的基因，之前被定位到 1q24-q32。它最近被克隆，并且发现几种种系突变易患 HPT-JT 综合征。我们对一个患有 HPT-JT 综合征的韩国家系的完整 HRPT2 编码序列和剪接连接区进行了测序，并鉴定了内含子 2 中的一种新种系突变 IVS2-1G>A，该突变导致该家系中 HPT-JT 综合征的常染色体显性特征。 RT-PCR 和转录本测序表明，这种剪接突变产生了选择性剪接错误，导致形成两种不同的转录本，一种删除了外显子 3，另一种由于在外显子 3 中使用了内部剪接受体而缺少外显子 3 的前 23 bp。两种转录本的翻译都会导致过早终止。此外，我们在受影响个体的恶性甲状旁腺肿瘤中检测到了两种新的 HRPT2 体细胞突变。一是85delG，导致提前终止；另一个是 13_30delCTTAGCGTCCTGCGACAG 的 18 bp 框内删除，表明该区域可能在 HPT-JT 综合征中甲状旁腺癌的发展中发挥重要作用。这些发现进一步证明HRPT2突变与HPT-JT综合征中甲状旁腺肿瘤的形成有关。
HRPT2, the gene associated with hyperparathyroidism-jaw tumor (HPT-JT) syndrome, was previously mapped to 1q24-q32. It was recently cloned, and several germline mutations were found to predispose to HPT-JT syndrome. We sequenced the complete HRPT2 coding sequence and splice-junctional regions in a Korean family with HPT-JT syndrome and identified a novel germline mutation, IVS2-1G>A in intron 2, that caused the autosomal dominant trait of HPT-JT syndrome in this family. RT-PCR and sequencing of the transcripts revealed that this splicing mutation generated alternative splicing errors leading to the formation of two different transcripts, one with exon 3 deleted, the other lacking the first 23 bp of exon 3 due to the use of an internal splice acceptor in exon 3. Translation of both transcripts results in premature termination. In addition, we detected two novel somatic mutations of HRPT2 in malignant parathyroid tumors from the affected individuals. One, 85delG, causes premature termination; the other, an 18 bp in-frame deletion of 13_30delCTTAGCGTCCTGCGACAG, suggests that this region may be important in the development of the parathyroid carcinomas in HPT-JT syndrome. These findings provide further evidence that mutation of HRPT2 is associated with the formation of parathyroid tumors in HPT-JT syndrome.
影响因子：
3.8
作者：
Charles E. Jackson;R. Norum;Boyd Sb;G. Talpos;Stuart D. Wilson;Taggart Rt;Mallette Le
通讯作者：
Charles E. Jackson;R. Norum;Boyd Sb;G. Talpos;Stuart D. Wilson;Taggart Rt;Mallette Le
影响因子：
9.8
作者：
József Szabó;Brett Heath;Virginia Hill;C. Jackson;R. Zarbo;L. Mallette;S. Chew;G. Besser;R. Thakker;V. Huff;M. Leppert;H. Heath
通讯作者：
József Szabó;Brett Heath;Virginia Hill;C. Jackson;R. Zarbo;L. Mallette;S. Chew;G. Besser;R. Thakker;V. Huff;M. Leppert;H. Heath