A novel <i>BMPR1A</i> mutation affects mRNA splicing in juvenile polyposis syndrome
A novel <i>BMPR1A</i> mutation affects mRNA splicing in juvenile polyposis syndrome
复制标题
一种新的<i>BMPR1A</i>突变影响幼年息肉病综合征中的mRNA剪接
DOI：
10.1111/ped.15041
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发表时间：
2022
影响因子：
1.4
通讯作者：
Takada Hidetoshi
中科院分区：
文献类型：
--
作者：
Imagawa Kazuo;Morita Atsushi;Fukushima Hiroko;Tagawa Manabu;Takada Hidetoshi
背景幼年息肉综合征是由于BMPR1 A和SMAD4基因突变导致转化生长因子β信号调节异常而引起的遗传性息肉综合征之一。携带SMAD4基因突变的青少年息肉综合征患者会发生心血管事件，而携带BMPR1A基因的患者通常不会。分析JPS患者的基因突变有助于制定适当的医疗管理策略。本研究利用从JPS患儿结肠粘膜中提取的mRNA，对BMPR1基因中一个新的内含子突变的致病性进行了研究。方法分别采用外周血基因组DNA和结肠粘膜总RNA进行DNA测序和逆转录聚合酶链式反应(RT-PCR)。结肠镜检查显示结肠内有多发性息肉，切除的息肉与幼年性息肉相容。测序分析发现BMPR1a存在一个新的内含子突变(c.778+5G>；C)。逆转录聚合酶链式反应分析从结肠粘膜提取的RNA显示BMPR1a的异常剪接形式。Trio分析显示，他的母亲也有相同的BMPR1基因突变。她在41岁时被诊断为盲肠癌和结肠息肉病。结论我们在一个JPS家系中发现了一种新的BMPR1内含子突变，该突变表现为剪接异常。进一步的研究和开发将有助于阐明JPS的基因型-表型关系。
BackgroundJuvenile polyposis syndrome (JPS) is one of the hereditary polyposis syndromes caused by abnormal regulation of transforming growth factor β signaling because of mutations inBMPR1AandSMAD4. Juvenile polyposis syndrome patients withSMAD4mutations develop cardiovascular events, whereas those withBMPR1Ausually do not. Analysis of genetic mutations in JPS patients can be helpful in devising suitable strategies for medical management. In this study, we demonstrate the pathogenicity of a novel intronic mutation inBMPR1Ausing mRNA extracted from colonic mucosa of a boy with JPS.MethodsGenomic DNA extracted from peripheral blood and total RNA isolated from the colonic mucosa were used for DNA sequencing and reverse transcription polymerase chain reaction (RT‐PCR) analyses, respectively.ResultsA 13‐year‐old boy, with no previous medical history, presented to the hospital complaining of bloody stools. Colonoscopy revealed multiple polyps in the colon, and the resected polyps were compatible with juvenile polyps. Sequencing analysis revealed a novel intronic mutation (c.778+5G>C) inBMPR1A. Reverse transcription polymerase chain reaction analysis of RNA extracted from the colonic mucosa showed an aberrant splicing form ofBMPR1A. Trio analysis showed that his mother also had the sameBMPR1Amutation. She was diagnosed with cancer of the cecum and polyposis of the colon at the age of 41.ConclusionWe demonstrate the presence of a novelBMPR1Aintronic mutation that exhibits splicing abnormality in a family with JPS. Further research and development will help elucidate the genotype–phenotype relationship in JPS.