The Invitae Autophagic Vacuolar Myopathy Panel analyzes three genes associated with autophagic vacuolar myopathy (AVM), a group of myopathies characterized by unusual autophagic vacuoles with sarcolemmal features and includes Danon disease and X-linked myopathy with excessive autophagy. These genes were curated based on current evidence to provide a comprehensive test for the genetic causes of AVM.
Individuals with clinical signs and symptoms of autophagic vacuolar myopathies may benefit from diagnostic genetic testing to confirm or establish a differential diagnosis, to provide anticipatory guidance, to help determine which relatives are at risk, or to guide enrollment in certain clinical trials.
DES LAMP2 VMA21
DES LAMP2 VMA21
Autophagic vacuolar myopathies (AVMs) are a group of muscle disorders histopathologically categorized by autophagic vacuoles containing both lysosomal and autophagosomal proteins, which are sometimes lined with sarcolemmal proteins such as dystrophin. The AVMs included in this panel are DES-related myopathy, Danon disease, and X-linked myopathy with excessive autophagy (XMEA). DES-related myopathy is characterized by slowly progressive weakness that involves proximal (25% of cases) and distal (80% of cases) skeletal muscles. Age of onset is variable from early childhood to late adulthood. Other features include peripheral neuropathy, present in about 20% of affected individuals, and cardiomyopathy, present in 15%-30% of cases. Danon disease is characterized by cardiomyopathy, arrhythmia, skeletal myopathy, and a varying degree of intellectual disability in males. Additional features may include retinal,liver, or pulmonary disease. Carrier females may also develop features of Danon disease. Age of onset is extremely variable, and child, adolescent, and adult onset cases have been reported in the literature. XMEA is characterized by predominantly childhood onset of progressive muscle weakness and atrophy primarily affecting the proximal muscles.
|Autosomal dominant||Autosomal recessive||X-linked|
|VMA21||✓||X-linked myopathy with excessive autophagy (XMEA)|
Due to the rarity of AVMs, the clinical sensitivity of this panel has not yet been established.
The DES gene is associated with both autosomal dominant and autosomal recessive myopathy. LAMP2-associated Danon disease and VMA21-associated XMEA are X-linked disorders.
Penetrance varies according to the causative gene. DES-related myopathies can present late in adulthood, which makes determination of penetrance difficult. LAMP2 is the only gene known to be associated with Danon disease, although some individuals can present with cardiomyopathy as the initial symptom, making determination of penetrance difficult (PMID:25228319). Incomplete penetrance has been reported for XMEA (PMID:15753448).
AVMs are a rare group of disorders, and the overall prevalence of these conditions is currently unknown.
The clinical spectrum of AVMs is broad. Several muscle disorders can have a similar phenotype and establishing a differential diagnosis may be crucial. Genetic testing may confirm a suspected diagnosis, narrow down the diagnosis to a specific type of AVM, or rule out disorders with similar symptoms. A genetic diagnosis may also help predict disease progression and inform recurrence risk.
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|