TY - JOUR
T1 - Modifier genes and their effect on Duchenne muscular dystrophy
AU - Vo, Andy H.
AU - McNally, Elizabeth M.
N1 - Publisher Copyright:
Copyright © 2015 Wolters Kluwer Health, Inc.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - Purpose of review Recently, genetic pathways that modify the clinical severity of Duchenne muscular dystrophy (DMD) have been identified. The pathways uncovered as modifiers are useful to predict prognosis and also elucidate molecular signatures that can be manipulated therapeutically. Recent findings Modifiers have been identified using combinations of transcriptome and genome profiling. Osteopontin, encoded by the SPP1 gene, was found using gene expression profiling. Latent TGFb binding protein 4, encoding latent TGFb binding protein 4 was initially discovered using a genome-wide screen in mice and then validated in cohorts of DMD patients. These two pathways converge in that they both regulate TGFb. A third modifier, Anxa6 that specifies annexin A6, is a calcium binding protein that has been identified using mouse models, and regulates the injury pathway and sarcolemmal resealing. Summary Genetic modifiers can serve as biomarkers for outcomes in DMD. Modifiers can alter strength and ambulation in muscular dystrophy, and these same features can be used as endpoints used in clinical trials. Moreover, because genetic modifiers can influence outcomes, these genetic markers should be considered when stratifying results in muscular dystrophy.
AB - Purpose of review Recently, genetic pathways that modify the clinical severity of Duchenne muscular dystrophy (DMD) have been identified. The pathways uncovered as modifiers are useful to predict prognosis and also elucidate molecular signatures that can be manipulated therapeutically. Recent findings Modifiers have been identified using combinations of transcriptome and genome profiling. Osteopontin, encoded by the SPP1 gene, was found using gene expression profiling. Latent TGFb binding protein 4, encoding latent TGFb binding protein 4 was initially discovered using a genome-wide screen in mice and then validated in cohorts of DMD patients. These two pathways converge in that they both regulate TGFb. A third modifier, Anxa6 that specifies annexin A6, is a calcium binding protein that has been identified using mouse models, and regulates the injury pathway and sarcolemmal resealing. Summary Genetic modifiers can serve as biomarkers for outcomes in DMD. Modifiers can alter strength and ambulation in muscular dystrophy, and these same features can be used as endpoints used in clinical trials. Moreover, because genetic modifiers can influence outcomes, these genetic markers should be considered when stratifying results in muscular dystrophy.
KW - Latent transforming growth factor β binding
KW - Muscular dystrophy
KW - Osteopontin
KW - Transforming growth factor β
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U2 - 10.1097/WCO.0000000000000240
DO - 10.1097/WCO.0000000000000240
M3 - Review article
C2 - 26263473
AN - SCOPUS:84941781335
VL - 28
SP - 528
EP - 534
JO - Current Opinion in Neurology
JF - Current Opinion in Neurology
SN - 1350-7540
IS - 5
ER -