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

Zimoń, Magdalena; Baets, Jonathan; Almeida-Souza, Leonardo; De Vriendt, Els; Nikodinovic, Jelena; Parman, Yesim; Battalo Gcaron Lu, Esra; Matur, Zeliha; Guergueltcheva, Velina; Tournev, Ivailo; Auer-Grumbach, Michaela; De Rijk, Peter; Petersen, Britt-Sabina; Müller, Thomas; Fransen, Erik; Van Damme, Philip; Löscher, Wolfgang N; Barišić, Nina; Mitrovic, Zoran; Previtali, Stefano C; Topalo Gcaron Lu, Haluk; Bernert, Günther; Beleza-Meireles, Ana; Todorovic, Slobodanka; Savic-Pavicevic, Dusanka; Ishpekova, Boryana; Lechner, Silvia; Peeters, Kristien; Ooms, Tinne; Hahn, Angelika F; Züchner, Stephan; Timmerman, Vincent; Van Dijck, Patrick; Rasic, Vedrana Milic; Janecke, Andreas R; De Jonghe, Peter; Jordanova, Albena

doi:10.1038/ng.2406

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

Author:

Zimoń, Magdalena

Baets, Jonathan ; Almeida-Souza, Leonardo ; De Vriendt, Els ; Nikodinovic, Jelena ; Parman, Yesim ; Battalo Gcaron Lu, Esra ; Matur, Zeliha ; Guergueltcheva, Velina ; Tournev, Ivailo ; Auer-Grumbach, Michaela ; De Rijk, Peter ; Petersen, Britt-Sabina ; Müller, Thomas ; Fransen, Erik ; Van Damme, Philip ; Löscher, Wolfgang N ; Barišić, Nina ; Mitrovic, Zoran ; Previtali, Stefano C ; Topalo Gcaron Lu, Haluk ; Bernert, Günther ; Beleza-Meireles, Ana ; Todorovic, Slobodanka ; Savic-Pavicevic, Dusanka ; Ishpekova, Boryana ; Lechner, Silvia ; Peeters, Kristien ; Ooms, Tinne ; Hahn, Angelika F ; Züchner, Stephan ; Timmerman, Vincent ; Van Dijck, Patrick ; Rasic, Vedrana Milic ; Janecke, Andreas R ; De Jonghe, Peter ; Jordanova, Albena

Keywords:

Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, GENERATED LYSYL-ADENYLATE, HISTIDINE, SUPPORTS, MICE, Abnormalities, Multiple, Amino Acid Sequence, Animals, Conserved Sequence, DNA Mutational Analysis, Gene Expression, Genes, Recessive, Genetic Association Studies, Genetic Complementation Test, Hereditary Sensory and Motor Neuropathy, Humans, Mice, Mutation, Missense, Myotonia, Nerve Tissue Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Syndrome, 06 Biological Sciences, 11 Medical and Health Sciences, Developmental Biology, 3001 Agricultural biotechnology, 3102 Bioinformatics and computational biology, 3105 Genetics

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.