SDHA突变引起多系统线粒体疾病:小说与遗传性肿瘤突变和基因重叠。
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Renkema GH, Wortmann某人,史密兹RJ Venselaar H,安东尼·M,维瑟克,Ben-Omran T, van den Heuvel LP timmer HJ, Smeitink是的,Rodenburg RJ
SDHA突变引起多系统线粒体疾病:小说与遗传性肿瘤突变和基因重叠。
欧元J哼麝猫。2015年2月,23 (2):202 - 9。doi: 10.1038 / ejhg.2014.80。Epub 2014年4月30日。
- PubMed ID
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24781757 (在PubMed]
- 文摘
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线粒体呼吸链的缺陷在复杂二世是一个罕见的线粒体疾病的原因。底层常染色体隐形遗传缺陷被发现在大多数的SDHx基因编码复杂二世(SDHA、SDHB SDHC和SDHD)及其装配因素。有趣的是,SDHx基因还函数作为遗传副神经节瘤的肿瘤抑制基因,嗜铬细胞瘤、胃肠道间质瘤。在这些情况下,受影响的病人的载体heterozygeous SDHx生殖系突变。直到现在,突变SDHx与线粒体疾病没有相关报道与遗传性肿瘤,反之亦然。在这里,我们描述四个隔离患者复杂二世不足引起的突变SDHA出现多系统线粒体疾病包括利综合征(LS)和/或脑白质营养不良。分子遗传分析显示三个小说在SDHA突变。两个突变(c。64 - 2 > G和c.1065-3C >)影响信使rna剪接,导致蛋白表达的损失。这是第一个突变描述影响SDHA拼接。 For the third new mutation, c.565T>G, we show that it severely affects enzyme activity. Its pathogenicity was confirmed by lentiviral complementation experiments on the fibroblasts of patients carrying this mutation. It is of special interest that one of our LS patients harbored the c.91C>T (p.Arg31*) mutation that was previously only reported in association with paragangliomas and pheochromocytomas, tightening the gap between these two rare disorders. As tumor screening is recommended for SDHx mutation carriers, this should also be considered for patients with mitochondrial disorders and their family members.