DES Mutation Analysis
Desmin is a type III intermediate filament protein that is expressed in skeletal, cardiac and smooth muscle cells. Desmin interacts with other intermediate filament proteins, as well as with microfilaments and microtubules, to form the cytoskeleton of the cell. In addition, desmin and other intermediate filament proteins work together to maintain the proper connection between the contractile apparatus and the cytoskeleton. Desmin is encoded by the gene DES, which is composed of nine exons and is located at 2q35.
Mutations in DES have been described for a spectrum of diseases. Desminopathy is typically characterized by distal muscle weakness and atrophy that usually begins in the lower limbs and spreads to the hands and arms, truncal, neck-flexor and sometimes facial muscles. Desminopathy can also result in swallowing and respiratory impairment. The spectrum of phenotypes resulting from desmin mutations is broad, ranging from skeletal myopathy with no cardiac involvement to skeletal myopathy with cardiomyopathy, to cardiomyopathy without skeletal muscle involvement. Cardiac manifestations can include dilated cardiomyopathy, arrhythmias and conduction block. Autosomal dominant and recessive DES mutations have been identified in this disease spectrum and include missense, nonsense, splicing and small deletion or insertion mutations.
The John Welsh Cardiovascular Diagnostic Laboratory offers molecular genetic testing for DES mutations. Individuals are tested by automatic fluorescent DNA sequencing of all nine exons of the DES gene. We strongly recommend initial testing of an affected individual, if available, in order to provide the greatest test sensitivity and clearest interpretation of results for subsequent family members. Genetic counseling is recommended for all individuals in order to identify additional at-risk family members and to discuss reproductive issues.
Reasons for Referral
Molecular confirmation of the diagnosis of desminopathy and/or dilated cardiomyopathy with conduction system disease
Genomic DNA is analyzed for DES mutations by automatic fluorescent DNA sequencing of all nine exons of the DES gene, as well as the exon/intron junctions and a portion of the 5′ and 3′ untranslated regions. Patient DNA is sequenced in both the forward and reverse orientations. If a mutation is identified, additional family members are analyzed only for the familial mutation(s) by automatic fluorescent DNA sequencing.
|Service||Direct and Institutional Billing||CPT Codes|
|Index Case (Male or Female)||$750 per sample||81405, G0452|
|Additional Family Members||$300 per sample; known familial mutation only||81403, G0452|
DNA Sequencing Analysis: Approximately 99 percent detection of mutations in exons 1-9 of DES.
Blood (preferred): EDTA (purple-top) tubes: Adult: 5 cc, Child: 5 cc, Infant: 2-3 cc
Tissue: Frozen (preferred), RNAlater, Formalin-fixed, Paraffin-embedded
Other Body Fluids: Call to inquire
Buccal Swabs: One swab from each cheek