Loss-of-function mutations in HINT1 cause axonal neuropathy with neuromyotonia.

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.

• Authors: Magdalena Zimoń, Jonathan Baets, Leonardo Almeida-Souza, Els De Vriendt, Jelena Nikodinovic, Yesim Parman, Esra Battaloğlu, Zeliha Matur, Velina Guergueltcheva, Ivailo Tournev, Michaela Auer-Grumbach, Peter De Rijk, Britt-Sabina Petersen, Thomas Müller, Erik Fransen, Philip Van Damme, Wolfgang N Löscher, Nina Barišić, Zoran Mitrovic, Stefano C Previtali, Haluk Topaloğlu, Günther Bernert, Ana Beleza-Meireles, Slobodanka Todorovic, Dusanka Savic-Pavicevic, Boryana Ishpekova, Silvia Lechner, Kristien Peeters, Tinne Ooms, Angelika F Hahn, Stephan Züchner, Vincent Timmerman, Patrick Van Dijck, Vedrana Milic Rasic, Andreas R Janecke, Peter De Jonghe, Albena Jordanova
• Journal: Nature genetics (Nat Genet) Vol. 44 Issue 10 Pg. 1080-3 (Oct 2012) ISSN: 1546-1718 [Electronic] United States
• PMID: 22961002 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• HINT1 protein, human
• Nerve Tissue Proteins
• Saccharomyces cerevisiae Proteins

Topics

• Abnormalities, Multiple (enzymology, genetics)
• Amino Acid Sequence
• Animals
• Conserved Sequence
• DNA Mutational Analysis
• Gene Expression
• Genes, Recessive
• Genetic Association Studies
• Genetic Complementation Test
• Hereditary Sensory and Motor Neuropathy (enzymology, genetics)
• Humans
• Mice
• Mutation, Missense
• Myotonia (enzymology, genetics)
• Nerve Tissue Proteins (genetics, metabolism)
• Saccharomyces cerevisiae (enzymology, genetics)
• Saccharomyces cerevisiae Proteins (genetics, metabolism)
• Syndrome