TY - JOUR
T1 - Navajo neurohepatopathy is caused by a mutation in the MPV17 gene
AU - Karadimas, Charalampos L.
AU - Vu, Tuan H.
AU - Holve, Stephen A.
AU - Chronopoulou, Penelope
AU - Quinzii, Catarina
AU - Johnsen, Stanley D.
AU - Kurth, Janice
AU - Eggers, Elizabeth
AU - Palenzuela, Lluis
AU - Tanji, Kurenai
AU - Bonilla, Eduardo
AU - De Vivo, Darryl C.
AU - DiMauro, Salvatore
AU - Hirano, Michio
N1 - Funding Information:
This work was supported by National Institutes of Health grants NS11766 and HD32062, by a grant from the Muscular Dystrophy Association, and by the Marriott Mitochondrial Disorder Clinical Research Fund and the Colleen Giblin Foundation.
PY - 2006/9
Y1 - 2006/9
N2 - 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.
AB - 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.
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U2 - 10.1086/506913
DO - 10.1086/506913
M3 - Article
C2 - 16909392
AN - SCOPUS:33748642169
SN - 0002-9297
VL - 79
SP - 544
EP - 548
JO - American journal of human genetics
JF - American journal of human genetics
IS - 3
ER -