Hereditary sensory autonomic neuropathy caused by a mutation in dystonin.

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.

• Authors: Simon Edvardson, Yuval Cinnamon, Chaim Jalas, Avraham Shaag, Channa Maayan, Felicia B Axelrod, Orly Elpeleg
• Journal: Annals of neurology (Ann Neurol) Vol. 71 Issue 4 Pg. 569-72 (Apr 2012) ISSN: 1531-8249 [Electronic] United States
• PMID: 22522446 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 American Neurological Association.

Chemical References

• Carrier Proteins
• Cytoskeletal Proteins
• DST protein, human
• Dystonin
• Nerve Tissue Proteins

Topics

• Base Sequence
• Carrier Proteins (genetics)
• Child, Preschool
• Chromosome Mapping
• Cytoskeletal Proteins (genetics)
• DNA Mutational Analysis
• Dystonin
• Female
• Genetic Predisposition to Disease
• Hereditary Sensory and Autonomic Neuropathies (genetics, pathology)
• Humans
• Infant
• Jews
• Male
• Microtubules (genetics, pathology)
• Molecular Sequence Data
• Mutation
• Nerve Tissue Proteins (genetics)
• Pedigree