Associated disorders

The DES gene is associated with autosomal dominant and recessive myofibrillar myopathy 1 (MFM1) (MedGen UID: 330449). It is also associated with autosomal recessive limb-girdle muscular dystrophy type 2R (LGMD2R)(MedGen UID: 815467) and autosomal dominant dilated cardiomyopathy (DCM) (MedGen UID: 387998).

Pathogenic variants in DES account for approximately 7% of known familial cases of myofibrillar myopathy, and the genetic cause is understood for only approximately half of all such cases. Pathogenic DES variants are a rare cause of limb-girdle muscular dystrophy.

DES encodes desmin, a cardiac and skeletal muscle protein that forms an intermediate filament connecting the contractile apparatus (by encircling the Z-band) to the sarcolemma and cytoplasmic organelles. Desmin functions to transmit force.

  1. Pugh TJ, et al. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. 2014 Genet Med Aug; 16(8):601-608. PMID: 24503780
  2. Hedberg, C, et al. Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy 7 is caused by a DES mutation. Eur. J. Hum. Genet. 2012; 20(9):984-5. doi: 10.1038/ejhg.2012.39. PMID: 22395865
  3. Muntoni, F, et al. Disease severity in dominant Emery Dreifuss is increased by mutations in both emerin and desmin proteins. Brain. 2006; 129(Pt 5):1260-8. doi: 10.1093/brain/awl062. PMID: 16585054
  4. Hong, D, et al. A series of Chinese patients with desminopathy associated with six novel and one reported mutations in the desmin gene. Neuropathol. Appl. Neurobiol. 2011; 37(3):257-70. doi: 10.1111/j.1365-2990.2010.01112.x. PMID: 20696008
  5. Dalakas, MC, et al. Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene. N. Engl. J. Med. 2000; 342(11):770-80. doi: 10.1056/NEJM200003163421104. PMID: 10717012
  6. McLaughlin, HM, et al. Compound heterozygosity of predicted loss-of-function DES variants in a family with recessive desminopathy. BMC Med. Genet. 2013; 14:68. doi: 10.1186/1471-2350-14-68. PMID: 23815709
  7. Selcen, D, Engel, AG. Myofibrillar Myopathy. 2005 Jan 28. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: PMID: 20301672
  8. Nigro, V, Savarese, M. Genetic basis of limb-girdle muscular dystrophies: the 2014 update. Acta Myol. 2014; 33(1):1-12. PMID: 24843229
  9. Selcen, D, et al. Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patients. Brain. 2004; 127(Pt 2):439-51. doi: 10.1093/brain/awh052. PMID: 14711882
  10. Selcen, D. Myofibrillar myopathies. Curr. Opin. Neurol. 2010; 23(5):477-81. doi: 10.1097/WCO.0b013e32833d38b0. PMID: 20664348
  11. Selcen, D. Myofibrillar myopathies. Neuromuscul. Disord. 2011; 21(3):161-71. doi: 10.1016/j.nmd.2010.12.007. PMID: 21256014

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
DES NM_001927.3