Purevsuren Jamiyan, Fukao Toshiyuki, Hasegawa Yuki, Fukuda Seiji, Kobayashi Hironori, Yamaguchi Seiji
Department of Pediatrics, Shimane University Faculty of Medicine, 89-1 Enya, Izumo, Shimane 693-8501, Japan.
Mol Genet Metab. 2008 Sep-Oct;95(1-2):46-51. doi: 10.1016/j.ymgme.2008.06.013. Epub 2008 Aug 9.
Mitochondrial trifunctional protein (MTP) comprises heterooctamer alpha4beta4 and a deficiency in this protein causes a mitochondrial long-chain beta-oxidation defect. Here, we describe the molecular basis of an MTPbeta-subunit deficiency in a Japanese neonate. Mutation screening at the genomic level including all exons and exon-intron boundaries identified a novel c.1136A>G (H346R) mutation in exon 13 of the maternal allele, but none in the paternal allele. Analysis by RT-PCR identified paternal-specific 106- and 56-bp intronic insertions between exons 7 and 8, which introduced premature terminations. This intronic exonization was caused by a deep intronic mutation in intron 7 on the paternal allele that generates a cryptic splice donor site. This is the first report of a deep intronic mutation in MTP deficiency.
线粒体三功能蛋白（MTP）由α4β4异源八聚体组成，该蛋白的缺陷会导致线粒体长链β氧化缺陷。在此，我们描述了一名日本新生儿中MTPβ亚基缺陷的分子基础。在基因组水平上对包括所有外显子和外显子-内含子边界进行的突变筛查，在母本等位基因的第13外显子中发现了一个新的c.1136A>G（H346R）突变，但父本等位基因中未发现。通过RT-PCR分析，在第7和第8外显子之间发现了父本特异性的106 bp和56 bp内含子插入，这导致了提前终止。这种内含子外显化是由父本等位基因第7内含子中的一个内含子深处突变引起的，该突变产生了一个隐蔽的剪接供体位点。这是关于MTP缺乏症中内含子深处突变的首次报道。
