Premium
Hereditary sensory autonomic neuropathy caused by a mutation in dystonin
Author(s) -
Edvardson Simon,
Cinnamon Yuval,
Jalas Chaim,
Shaag Avraham,
Maayan Channa,
Axelrod Felicia B.,
Elpeleg Orly
Publication year - 2012
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.23524
Subject(s) - familial dysautonomia , exome sequencing , dysautonomia , genetics , mutation , exome , biology , downregulation and upregulation , dystonia , gene , medicine , bioinformatics , neuroscience , disease
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;71:569–572