title: 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.affiliation: Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Simon
authors.initials: S
authors.lastname: Edvardson
authors.forename: Yuval
authors.initials: Y
authors.lastname: Cinnamon
authors.forename: Chaim
authors.initials: C
authors.lastname: Jalas
authors.forename: Avraham
authors.initials: A
authors.lastname: Shaag
authors.forename: Channa
authors.initials: C
authors.lastname: Maayan
authors.forename: Felicia B
authors.initials: FB
authors.lastname: Axelrod
authors.forename: Orly
authors.initials: O
authors.lastname: Elpeleg
mesh_terms: D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002675:Child, Preschool; D002874:Chromosome Mapping; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D000071821:Dystonin; D005260:Female; D020022:Genetic Predisposition to Disease; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D007585:Jews; D008297:Male; D008870:Microtubules / Q000235:genetics / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C486268:DST protein, human; D000071821:Dystonin; D009419:Nerve Tissue Proteins