Biomedical Engineering Reference
The NMD NGS panels offer cost-effective and more rapid molecular diagnostic
testing than the conventional sequential Sanger sequencing of associated genes.
A faster molecular diagnosis of NMD will have major impacts on patients as it will
improve disease management and genetic counseling, and will allow access to ther-
apy or inclusion into therapeutic trials. However, the targeted sequencing strategy
has limitations. As the current methods did not equal Sanger sequencing in terms of
analytical sensitivity and specifi city, mainly because of insuffi cient coverage of tar-
get regions, complementary Sanger sequencing seems to be necessary. Furthermore,
for the application of this approach to be used in clinical molecular diagnostics, the
analytical sensitivity and specifi city need to be determined according to the indi-
vidualized target enrichment methods and sequencing platforms.
Bennett RR, den Dunnen J, O'Brien KF et al (2001) Detection of mutations in the dystrophin gene
via automated DHPLC screening and direct sequencing. BMC Genet 2:17
Emery AE (1991) Population frequencies of inherited neuromuscular diseases—a world survey.
Neuromuscul Disord 1:19-29
Flanigan KM, von Niederhausern A, Dunn DM et al (2003) Rapid direct sequence analysis of the
dystrophin gene. Am J Hum Genet 72:931-939
Hackman P, Vihola A, Haravuori H et al (2002) Tibial muscular dystrophy is a titinopathy caused
by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin. Am J Hum
Lalic T, Vossen RHAM, Coffa J et al (2005) Deletion and duplication screening in the DMD gene
Lim BC, Lee S, Shin J-Y et al (2011) Genetic diagnosis of Duchenne and Becker muscular dystro-
phy using next-generation sequencing technology: comprehensive mutational search in a single
platform. J Med Genet 48:731-736. doi: 10.1136/jmedgenet-2011-100133
Mendell JR, Buzin CH, Feng J et al (2001) Diagnosis of Duchenne dystrophy by enhanced detec-
tion of small mutations. Neurology 57:645-650
North K (2008) What's new in congenital myopathies? Neuromuscul Disord 18:433-442.
Prior TW, Bridgeman SJ (2005) Experience and strategy for the molecular testing of Duchenne
muscular dystrophy. J Mol Diagn 7:317-326. doi: 10.1016/S1525-1578(10)60560-0
Sironi M, Pozzoli U, Comi GP et al (2006) A region in the dystrophin gene major hot spot harbors
a cluster of deletion breakpoints and generates double-strand breaks in yeast. FASEB
J 20:1910-1912. doi: 10.1096/fj.05-5635fje
Valencia CA, Rhodenizer D, Bhide S et al (2012) Assessment of target enrichment platforms using
massively parallel sequencing for the mutation detection for congenital muscular dystrophy.
J Mol Diagn 14:233-246. doi: 10.1016/j.jmoldx.2012.01.009
Valencia CA, Ankala A, Rhodenizer D et al (2013) Comprehensive mutation analysis for congeni-
tal muscular dystrophy: a clinical PCR-based enrichment and next-generation sequencing
panel. PLoS One 8:e53083. doi: 10.1371/journal.pone.0053083
Vasli N, Böhm J, Le Gras S et al (2012) Next-generation sequencing for molecular diagnosis of
neuromuscular diseases. Acta Neuropathol (Berl) 124:273-283. doi: 10.1007/s00401-012-0982-8