Abstract
Inherited peripheral neuropathies are frequent neuromuscular disorders known for their clinical and genetic heterogeneity. In 33 families, we identified 8 mutations in HINT1 (encoding histidine triad nucleotide-binding protein 1) by combining linkage analyses with next-generation sequencing and subsequent cohort screening of affected individuals. Our study provides evidence that loss of functional HINT1 protein results in a distinct phenotype of autosomal recessive axonal neuropathy with neuromyotonia.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Abnormalities, Multiple / enzymology
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Abnormalities, Multiple / genetics*
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Amino Acid Sequence
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Animals
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Conserved Sequence
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DNA Mutational Analysis
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Gene Expression
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Genes, Recessive
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Genetic Association Studies
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Genetic Complementation Test
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Hereditary Sensory and Motor Neuropathy / enzymology
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Hereditary Sensory and Motor Neuropathy / genetics*
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Humans
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Mice
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Mutation, Missense*
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Myotonia / enzymology
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Myotonia / genetics*
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism
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Saccharomyces cerevisiae / enzymology
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Syndrome
Substances
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HINT1 protein, human
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Nerve Tissue Proteins
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Saccharomyces cerevisiae Proteins