Transfer of a mitochondrial DNA fragment to MCOLN1 causes an inherited case of mucoliplidosis IV
Transfer of a mitochondrial DNA fragment to MCOLN1 causes an inherited case of mucoliplidosis IV
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DOI：
10.1002/humu.20094
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发表时间：
2004-01-01
期刊：
影响因子：
3.9
通讯作者：
Schiffmann, R
中科院分区：
文献类型：
--
作者：
Goldin, E;Stahl, S;Schiffmann, R
MCOLN 1中两个突变杂合的粘脂增多症-IV患者仅表达其父亲的cDNA突变c.1207C>T，预测粘脂中的R403 C改变。她从母亲那里继承了线粒体NADH脱氢酶5（MTND 5）的一个93 bp片段，该片段插入MCOLN 1外显子2的最后一个核苷酸之前的第一个框（c.236（-）237 ins 93）。这种改变破坏了MCOLN 1的正确剪接。由于插入片段的抑制作用，未使用外显子末端的剪接位点，导致在下游内含子中含有终止密码子的两种异常剪接产物。这些产物通过无义介导的衰变被消除。这是第一个报告的遗传转移线粒体核DNA导致遗传疾病。通过线粒体DNA消除剪接位点需要改变剪接预测模型。(C)2004 Wiley-Liss，Inc.
A patient with mucolipidosis-IV heterozygous for two mutations in MCOLN1 expressed only her father's cDNA mutation c.1207C>T predicting an R403C change in mucolipin. She inherited a 93bp segment from mitochondrial NADH dehydrogenase 5 (MTND5) from her mother that was inserted in,frame prior to the last nucleotide of exon 2 of MCOLN1 (c.236(-)237ins93). This alteration abolished proper splicing of MCOLN1. The splice site at the end of the exon was not used due to an inhibitory effect of the inserted segment, resulting in two aberrant splice products containing stop codons in the downstream intron. These products were eliminated via nonsense-mediated decay. This is the first report of an inherited transfer of mitochondrial nuclear DNA causing a genetic disease. The elimination of the splice site by the mitochondrial DNA requires a change in splicing prediction models. (C) 2004 Wiley-Liss, Inc.