The molecular basis of familial dysautonomia: overview, new discoveries and implications for directed therapies.

Abstract

Familial dysautonomia (FD) is a sensory and autonomic neuropathy that affects the development and survival of sensory, sympathetic, and some parasympathetic neurons. It is autosomally inherited and occurs almost exclusively among individuals of Ashkenazi Jewish descent. The pathological and clinical manifestations of FD have been extensively studied and therapeutic modalities have, until recently, focused primarily on addressing the symptoms experienced by those with this fatal disorder. The primary FD-causing mutation is an intronic nucleotide substitution that alters the splicing of the IKBKAP-derived transcript. Recent efforts have resulted in the development of new therapeutic modalities that facilitate the increased production of the correctly spliced transcript and mitigate the symptoms of those with FD. Furthermore, the recent demonstration of the reduced presence of monoamine oxidase A in cells and tissues of individuals with FD has provided new insight into the cause of hypertensive crises experienced by these patients.

• Authors: Berish Y Rubin, Sylvia L Anderson
• Journal: Neuromolecular medicine (Neuromolecular Med) Vol. 10 Issue 3 Pg. 148-56 ( 2008) ISSN: 1559-1174 [Electronic] United States
• PMID: 17985250 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Carrier Proteins
• Catecholamines
• Elp1 protein, human
• Transcriptional Elongation Factors
• Monoamine Oxidase

Topics

• Amino Acid Sequence
• Carrier Proteins (genetics, metabolism)
• Catecholamines (metabolism)
• Dysautonomia, Familial (genetics, physiopathology, therapy)
• Humans
• Molecular Sequence Data
• Monoamine Oxidase (deficiency)
• Mutation
• RNA Splicing
• Transcriptional Elongation Factors