title: Navajo neurohepatopathy is caused by a mutation in the MPV17 gene.
abstract: 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.
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Charalampos L
authors.initials: CL
authors.lastname: Karadimas
authors.forename: Tuan H
authors.initials: TH
authors.lastname: Vu
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Holve
authors.forename: Penelope
authors.initials: P
authors.lastname: Chronopoulou
authors.forename: Catarina
authors.initials: C
authors.lastname: Quinzii
authors.forename: Stanley D
authors.initials: SD
authors.lastname: Johnsen
authors.forename: Janice
authors.initials: J
authors.lastname: Kurth
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Eggers
authors.forename: Lluis
authors.initials: L
authors.lastname: Palenzuela
authors.forename: Kurenai
authors.initials: K
authors.lastname: Tanji
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bonilla
authors.forename: Darryl C
authors.initials: DC
authors.lastname: De Vivo
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
mesh_terms: D000328:Adult; D001927:Brain Diseases / Q000208:ethnology / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D003316:Corneal Diseases / Q000208:ethnology / Q000235:genetics*; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics; D005260:Female; D050259:Genes, Mitochondrial; D006720:Homozygote; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008099:Liver / Q000737:chemistry; D008107:Liver Diseases / Q000208:ethnology / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D010523:Peripheral Nervous System Diseases / Q000208:ethnology / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial