The genetics of spinal muscular atrophies

Research output: Contribution to journalArticle

Abstract

Purpose of review: This article reviews clinical, genetic, and therapeutic advances in spinal muscular atrophies (SMAs), inherited disorders characterized by motor neuron loss and muscle weakness. Recent findings: There has been progress in defining the clinical and genetic features of at least 16 distinct forms of SMA. The genes associated with 14 of these disorders have been identified in the last decade, including four within the last year: TRPV4, ATP7A, VRK1, and HSPB3. Genetic testing is now available for many SMAs, providing important diagnostic and prognostic information. Cell and animal models of SMAs have been used to further understand how mutations in SMA-associated genes, which code for proteins involved in diverse functions such as transcriptional regulation, RNA processing, and cytoskeletal dynamics, lead to motor neuron dysfunction and loss. In the last year, there has also been remarkable progress in preclinical therapeutics development for proximal SMA using gene therapy, antisense oligonucleotides, and small molecules. Summary: The advances in the clinical and genetic characterization of different forms of SMAs have important implications for clinical evaluation and management of patients. The identification of multiple, novel SMA-causing genes will lead to an improved understanding of motor neuron disease biology and may provide novel targets for therapeutics development.

Original languageEnglish (US)
Pages (from-to)450-458
Number of pages9
JournalCurrent Opinion in Neurology
Volume23
Issue number5
DOIs
StatePublished - Oct 2010

Fingerprint

Spinal Muscular Atrophy
Motor Neurons
Genes
Motor Neuron Disease
Antisense Oligonucleotides
Muscle Weakness
Genetic Testing
Genetic Therapy
Therapeutics
Animal Models
RNA
Mutation

Keywords

  • anterior horn cell
  • hereditary motor neuropathy
  • spinal and bulbar muscular atrophy
  • spinal muscular atrophy

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

The genetics of spinal muscular atrophies. / Wee, Claribel D.; Kong, Lingling; Sumner, Charlotte.

In: Current Opinion in Neurology, Vol. 23, No. 5, 10.2010, p. 450-458.

Research output: Contribution to journalArticle

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