Familial dysautonomia

Mechanisms and models

Research output: Contribution to journalReview article

15 Citations (Scopus)

Abstract

Hereditary Sensory and Autonomic Neuropathies (HSANs) compose a heterogeneous group of genetic disorders characterized by sensory and autonomic dysfunctions. Familial Dysautonomia (FD), also known as HSAN III, is an autosomal recessive disorder that affects 1/3,600 live births in the Ashkenazi Jewish population. The major features of the disease are already present at birth and are attributed to abnormal development and progressive degeneration of the sensory and autonomic nervous systems. Despite clinical interventions, the disease is inevitably fatal. FD is caused by a point mutation in intron 20 of the IKBKAP gene that results in severe reduction in expression of IKAP, its encoded protein. In vitro and in vivo studies have shown that IKAP is involved in multiple intracellular processes, and suggest that failed target innervation and/or impaired neurotrophic retrograde transport are the primary causes of neuronal cell death in FD. However, FD is far more complex, and appears to affect several other organs and systems in addition to the peripheral nervous system. With the recent generation of mouse models that recapitulate the molecular and pathological features of the disease, it is now possible to further investigate the mechanisms underlying different aspects of the disorder, and to test novel therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)497-514
Number of pages18
JournalGenetics and Molecular Biology
Volume39
Issue number4
DOIs
StatePublished - Oct 1 2016

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Familial Dysautonomia
Hereditary Sensory and Autonomic Neuropathies
Inborn Genetic Diseases
Molecular Models
Autonomic Nervous System
Peripheral Nervous System
Live Birth
Point Mutation
Introns
Cell Death
Parturition
Population
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics

Cite this

Familial dysautonomia : Mechanisms and models. / Dietrich, Paula; Dragatsis, Ioannis.

In: Genetics and Molecular Biology, Vol. 39, No. 4, 01.10.2016, p. 497-514.

Research output: Contribution to journalReview article

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