Hereditary sensory autonomic neuropathy caused by a mutation in dystonin
- 9 January 2012
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 71 (4), 569-572
- https://doi.org/10.1002/ana.23524
Abstract
In 4 infants with a new lethal autonomic sensory neuropathy with clinical features similar to familial dysautonomia as well as contractures, we identified a deleterious mutation in the DST gene, using homozygosity mapping followed by exome sequencing. DST encodes dystonin, a cytoskeleton linker protein, and the mutation results in an unstable transcript. Interestingly, dystonin is significantly more abundant in cells of familial dysautonomia patients with IKBKAP (I-κ-B kinase complex-associated protein) mutation compared to fibroblasts of controls, suggesting that upregulation of dystonin is responsible for the milder course in familial dysautonomia. Homozygosity mapping followed by exome sequencing is a successful approach to identify mutated genes in rare monogenic disorders. Ann Neurol 2012;71:569–572This publication has 16 references indexed in Scilit:
- Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing lossNature Genetics, 2011
- IKAP/Elp1 involvement in cytoskeleton regulation and implication for familial dysautonomiaHuman Molecular Genetics, 2011
- Diagnosis and new treatments in genetic neuropathiesJournal of Neurology, Neurosurgery & Psychiatry, 2009
- Elongator Controls the Migration and Differentiation of Cortical Neurons through Acetylation of α-TubulinCell, 2009
- Runs of homozygosity in European populationsAmerican Journal of Human Genetics, 2008
- Deleterious Mutation in the Mitochondrial Arginyl–Transfer RNA Synthetase Gene Is Associated with Pontocerebellar HypoplasiaAmerican Journal of Human Genetics, 2007
- Dystonin/Bpag1—A link to what?Cell Motility, 2007
- Inherited Autonomic NeuropathiesSeminars in Neurology, 2003
- Purification and Characterization of the Human Elongator ComplexOnline Journal of Public Health Informatics, 2002
- An Essential Cytoskeletal Linker Protein Connecting Actin Microfilaments to Intermediate FilamentsCell, 1996