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首页> 外文期刊>Journal of human genetics >Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD).
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Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD).

机译：线粒体天冬氨酸谷氨酸携带者（柠檬酸）缺乏症是成人发病的II型瓜氨酸血症（CTLN2）和特发性新生儿肝炎（NICCD）的原因。

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By using homozygosity mapping and positional cloning, we have shown that adult-onset type II citrullinemia (CTLN2) is caused by mutations of the SLC25A13 gene, which is localized on chromosome 7q21.3 and encodes a mitochondrial solute carrier protein named citrin. So far, we have reported nine mutations, most of which cause loss of citrin, and we have established several methods for DNA diagnosis. These methods have shown that more than 90% of the patients diagnosed as suffering from CTLN2 by enzymatic analysis carry SLC25A13 mutations in both alleles, indicating that CTLN2 is caused by citrin deficiency. Furthermore, by using the same DNA diagnosis methods, we discovered that 70 neonates or infants suffering from a particular type of neonatal hepatitis carry the same SLC25A13 mutations. Since the symptoms of the neonates are different from those of the more severe CTLN2 and usually ameliorate without special treatment, we designated the neonatal disease neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). We conclude that citrin deficiency causes NICCD in neonates and CTLN2 in adults through the additional effects of genetic or environmental modifiers. Since the function of citrin, together with that of an isoform, aralar, was found to be as a mitochondrial aspartate glutamate carrier, the various symptoms of NICCD and CTLN2 may be understood as caused by defective aspartate export from the mitochondria to the cytosol and defects in the malate aspartate shuttle. It is, however, still difficult to understand the cause of the hepatic deficiency of argininosuccinate synthetase protein in CTLN2.
机译：通过使用纯合性作图和位置克隆，我们已经显示，成年发作的II型瓜氨酸血症（CTLN2）是由SLC25A13基因的突变引起的，该基因位于染色体7q21.3上，并编码称为柠檬酸的线粒体溶质载体蛋白。到目前为止，我们已经报告了九种突变，其中大多数会导致柠檬酸的丢失，并且我们已经建立了几种DNA诊断方法。这些方法已经显示，通过酶促分析诊断为患有CTLN2的患者中，超过90％的患者在两个等位基因中均携带SLC25A13突变，表明CTLN2是由柠檬素缺乏引起的。此外，通过使用相同的DNA诊断方法，我们发现患有特殊类型的新生儿肝炎的70名新生儿或婴儿携带相同的SLC25A13突变。由于新生儿的症状与更严重的CTLN2的症状不同，并且通常无需特殊治疗即可缓解，因此我们将新生儿疾病称为由柠檬酸缺乏引起的新生儿肝内胆汁淤积症（NICCD）。我们得出的结论是，柠檬酸缺乏会通过遗传或环境修饰剂的额外作用导致新生儿NICCD和成人CTLN2。由于发现柠檬酸及其同工型aralar具有线粒体天冬氨酸谷氨酸载体的功能，因此NICCD和CTLN2的各种症状可能被理解为是由于天冬氨酸从线粒体向细胞质的出口缺陷所致。在苹果酸门冬氨酸穿梭中。然而，仍然难以理解CTLN2中精氨琥珀酸合成酶蛋白肝功能不足的原因。

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