The genetics of spinal muscular atrophies.
OBJECTIVE
This article reviews clinical, genetic, and therapeutic advances in spinal muscular atrophies (SMAs), inherited disorders characterized by motor neuron loss and muscle weakness.


RESULTS
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.


CONCLUSIONS
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.
Wee
Claribel D
CD
Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Kong
Lingling
L
Sumner
Charlotte J
CJ
D003937:Diagnosis, Differential; D006801:Humans; D009046:Motor Neurons / Q000502:physiology; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics
D009419:Nerve Tissue Proteins