Abstract:
:Malignant hyperthermia (MH)-related mutations have been identified in the ryanodine receptor type 1 gene (RYR1) and in the dihydropyridine gene (CACNA1S), but about half of the patients do not have causative mutations in these genes. We wanted to study the contribution of other muscle genes to the RYR1 phenotypes. We designed a gene panel for sequence enrichment targeting 64 genes of proteins involved in the homeostasis of the striated muscle cell. Next-generation sequencing (NGS) resulted in >50,000 sequence variants which were further analyzed by software filtering criteria to identify causative variants. In four of five patients we identified previously reported RYR1 mutations while the fifth patient did not show any candidate variant in any of the genes investigated. In two patients pathogenic variants were found in other genes known to cause a muscle disorders. All but one patient carried likely benign rare polymorphisms. The NGS technique proved convenient in identifying variants in the RYR1. However, with a clinically variable phenotype-like MH, the pre-selection of genes poses problems in variant interpretation.
journal_name
Clin Genetjournal_title
Clinical geneticsauthors
Broman M,Kleinschnitz I,Bach JE,Rost S,Islander G,Müller CRdoi
10.1111/cge.12508subject
Has Abstractpub_date
2015-10-01 00:00:00pages
381-5issue
4eissn
0009-9163issn
1399-0004journal_volume
88pub_type
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