Abstract
The practical basis for massive parallel sequencing is described to help clinicians
in choosing the most adequate diagnostic approach for childhood myopathies. The key
quality feature for massive parallel sequencing is the sequence depth (coverage) as
a prerequisite for variant identification and quantification of sequence copy numbers.
Our experience with a next-generation sequencing gene panel for the analysis of muscular
dystrophies/myopathies with infantile or juvenile onset resulted in the identification
of pathogenic or likely pathogenic mutations in approximately 41% (of 141 patients),
thus leading to a definitive diagnosis. A subset of patients shows an accumulation
of “excess” heterozygous variants that may act as modifiers of the phenotype. Massive
parallel sequencing has become a reliable and cost-effective method, but it requires
exact clinical, bioptic, and/or radiologic information to evaluate the clinical relevance
of possibly pathologic variants.
Keywords
congenital myopathy/muscular dystrophy - infantile myopathies/muscular dystrophies
- gene panel analysis - variant classification
