Navajo neurohepatopathy is caused by a mutation in the MPV17 gene
Navajo neurohepatopathy is caused by a mutation in the MPV17 gene
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DOI：
10.1086/506913
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发表时间：
2006-09-01
影响因子：
9.8
通讯作者：
Hirano, Michio
中科院分区：
文献类型：
--
作者：
Karadimas, Charalampos L.;Vu, Tuan H.;Hirano, Michio
纳瓦霍神经肝病（NNH）是一种常染色体隐性遗传疾病，在美国西南部的纳瓦霍儿童中流行。主要临床特征是肝病、周围神经病、角膜麻醉和疤痕、肢端残肢、脑白质脑病、发育迟缓以及并发感染的复发性代谢性酸中毒。婴儿期、儿童期和经典形式的 NNH 已被描述。在两名患者的肝脏中检测到线粒体 DNA (mtDNA) 耗尽，表明 mtDNA 维持存在主要缺陷。具有 NNH 的两个家族的纯合性作图表明与染色体 2p24 存在连锁。该基因座包括 MPV17 基因，该基因突变后会导致肝脑形式的 mtDNA 耗竭。对来自 5 个家庭的 6 名 NNH 患者的 MPV17 基因进行测序，发现存在其他地方描述的纯合 R50Q 突变。 NNH 患者中单个错义突变的鉴定证实该疾病可能是由于创始人效应造成的，并扩展了与 MPV17 突变相关的表型谱。
Navajo neurohepatopathy (NNH) is an autosomal recessive disease that is prevalent among Navajo children in the southwestern United States. The major clinical features are hepatopathy, peripheral neuropathy, corneal anesthesia and scarring, acral mutilation, cerebral leukoencephalopathy, failure to thrive, and recurrent metabolic acidosis with intercurrent infections. Infantile, childhood, and classic forms of NNH have been described. Mitochondrial DNA ( mtDNA) depletion was detected in the livers of two patients, suggesting a primary defect in mtDNA maintenance. Homozygosity mapping of two families with NNH suggested linkage to chromosome 2p24. This locus includes the MPV17 gene, which, when mutated, causes a hepatocerebral form of mtDNA depletion. Sequencing of the MPV17 gene in six patients with NNH from five families revealed the homozygous R50Q mutation described elsewhere. Identification of a single missense mutation in patients with NNH confirms that the disease is probably due to a founder effect and extends the phenotypic spectrum associated with MPV17 mutations.