Navajo Neurohepatopathy Is Caused by a Mutation in the MPV17 Gene

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 t...

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Bibliographic Details
Published in:American journal of human genetics 2006-09, Vol.79 (3), p.544-548
Main Authors: Karadimas, Charalampos L., Vu, Tuan H., Holve, Stephen A., Chronopoulou, Penelope, Quinzii, Catarina, Johnsen, Stanley D., Kurth, Janice, Eggers, Elizabeth, Palenzuela, Lluis, Tanji, Kurenai, Bonilla, Eduardo, De Vivo, Darryl C., DiMauro, Salvatore, Hirano, Michio
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Brain Diseases - ethnology
Brain Diseases - genetics
Chromosomes
Chromosomes, Human, Pair 2 - genetics
Corneal Diseases - ethnology
Corneal Diseases - genetics
DNA Mutational Analysis
DNA, Mitochondrial - analysis
DNA, Mitochondrial - genetics
Female
Gene loci
General aspects. Genetic counseling
Genes, Mitochondrial
Genetic linkage
Genotype & phenotype
Homozygote
Humans
Indians, North American - genetics
Liver - chemistry
Liver Diseases - ethnology
Liver Diseases - genetics
Male
Medical genetics
Medical sciences
Mitochondrial DNA
Mutation
Pedigree
Peripheral Nervous System Diseases - ethnology
Peripheral Nervous System Diseases - genetics
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Summary: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.
ISSN:0002-9297
1537-6605
DOI:10.1086/506913