Abstract
Genetic testing provides critical information for diagnosis, prognosis, and medical management in neuromuscular disease, but clinicians must be aware of the appropriate use, limitations, and utility of testing options. Recognition of common patterns of inheritance and exceptions to these patterns may help in identifying appropriate tests. In addition, an understanding of the common types of mutations in specific diseases and the methodologies employed to detect these mutations is critical. Newer sequencing methodologies enable clinicians to query large numbers of genes in patients with atypical clinical presentations, but interpretation of the DNA variants identified by these methods remains a challenge.
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Abbreviations
- AD:
-
Autosomal dominant
- AR:
-
Autosomal recessive
- NGS:
-
Next-generation sequencing
- WES:
-
Whole exome sequencing
- WGS:
-
Whole genome sequencing
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Gene reviews is a collection of expert-authored and peer-reviewed clinical synopses of inherited conditions. At present, there are 679 “chapters” each focused on a specific genetic disease or phenotype.
Human Genome Variation Society nomenclature guidelines: This website has published standard mutation nomenclature guidelines used to accurately describe DNA, RNA, and protein variants in databases, clinical reports, and publications. In addition, this website has links to locus-specific databases that are maintained independently of ClinVar and LOVD.
Genome Aggregation Database (gnomAD): Allele frequencies in control database comprised of >140,000 individuals. This is the largest publically available database of its type. At the time of this publication, this resource was still under development.
Exome Aggregation Consortium (ExAC): This is the predecessor to gnomAD, with exome data from >60,000 individuals. Much of the data are being rolled into the larger gnomAD database, but ExAC currently has some data not yet available in gnomAD such as exon-level copy number variation data.
ClinVar: This is a public database of variants and clinical assertions (pathogenic vs. benign). Submissions may be accompanied by varying types and amounts of evidence supporting the clinical assertion.
Leiden Open Variation Database is similar to ClinVar but based in Leiden University in the Netherlands. Data are organized by specific genes. The Leiden database has a long history of cataloging normal and pathogenic variation in neuromuscular disease genes.
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Bower, M. (2018). Genetic Testing in Neuromuscular Disease. In: Walk, D. (eds) Clinical Handbook of Neuromuscular Medicine . Springer, Cham. https://doi.org/10.1007/978-3-319-67116-1_10
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DOI: https://doi.org/10.1007/978-3-319-67116-1_10
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