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Myofibrillar Myopathy via the CRYAB Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
9207 CRYAB 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9207CRYAB81479 81479,81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Alpha-B crystallinopathy (OMIM 608810) encompasses disorders of skeletal and cardiac muscle as well as the eye. Myofibrillar myopathy (MFM) refers to a genetically heterogeneous group of disorders sharing a homogeneous morphological pattern with onset of symptoms in adulthood or very early in life. Stained with trichrome, abnormal muscle fibers are seen containing hyaline structures and vacuoles with membrane fragments from disintegrated sarcomeric Z disc and myofibrils (Selcen et al. Brain 127:439-451, 2004). With electron microscopy, affected muscle fibers reveal progressive degeneration of myofibrils beginning at the Z-disk. Immunohistochemical staining of the structurally abnormal fibers reveals abnormal expression and accumulation of several proteins, including myotilin, desmin, alpha-B crystalline, dystrophin and β-amyloid precursor protein (Selcen et al. 2004). Patients with classic myofibrillar myopathy present in adulthood with proximal and distal weakness and in some cases with cardiomyopathy. A variant of this disorder presents very early in life with severe and rapidly progressive symptoms including respiratory stress and progressive rigidity. Onset of symptoms are reported as early as four months of age (Forrest et al. Neuromuscul Disord 21, 37-40 2011) with death by age three (Del Bigio et al. Ann Neurol 69:866-871, 2011). Immunohistology is remarkable for presence of inclusion bodies with reactivity to the N-terminus but not the C-terminus of alpha B crystalline (Moore at al. J Neuropathol Exp Neurol 71:587-588, 2012). Other allelic disorders include dilated cardiomyopathy (Inagaki et al. Biochem Biophys Res Commun 342:379-386, 2006) and autosomal dominant congenital posterior cataract (Berry et al. Amer J Hum Genet 69:1141-1145, 2001; Liu et al. Invest Ophthalmol Vis Sci 47:1069-1075, 2006). Two cases of multisystem disease involving myofibrillar myopathy, cardiomyopathy, and cataract have also been reported (Vicart et al. Nat Genet 20:92-95, 1998; Sacconi et al. Neuromuscul Disord 2012 22:66-72, 2012).

Genetics

Adult-onset alpha-B crystalline-related myofibrillar myopathy, cardiomyopathy, and congenital posterior cataract are inherited as autosomal dominant disorders. Progressive, severe, congenital myopathy due to CRYAB variants is inherited as an autosomal recessive disorder and all cases reported thus far have had truncating variants. The c.60delC variant is considered a founder variant among Canadian aboriginals of Cree descent (Del Bigio et al. 2011). A small number of CRYAB missense, nonsense, and small deletion variants have been reported in patients with MFM (Selcen and Engel, GeneReviews 2010). Other genes involved with MFM include DES, MYOT, FLNC, LDB3, and BAG3.

Clinical Sensitivity - Sequencing with CNV PGxome

Adult-onset and congenital myofibrillar myopathy due to CRYAB variants are rare disorders. Among a cohort of 80 MFM patients diagnosed at the Mayo Clinic, 46% have been found to have variants in one of the six known causative genes, including 3% in CRYAB (Selcen and Engel, 2010).

Testing Strategy

This test provides full coverage of all coding exons of the CRYAB gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Patients with clinical features consistent with myofibrillar myopathy or early-onset, severe myopathy with rigidity.

Gene

Official Gene Symbol OMIM ID
CRYAB 123590
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Alpha-B Crystallinopathy AD 608810

Related Tests

Name
Comprehensive Cardiology Panel
Congenital Cataracts and Ayme-Gripp Syndrome via the MAF Gene

Citations

  • Berry, V., et.al. (2001). "Alpha-B crystallin gene (CRYAB) mutation causes dominant congenital posterior polar cataract in humans." Am J Hum Genet 69(5): 1141-5. PubMed ID: 11577372
  • Del Bigio, M. R., et.al. (2011). "Infantile muscular dystrophy in Canadian aboriginals is an alphaB-crystallinopathy." Ann Neurol 69(5): 866-71. PubMed ID: 21337604
  • Duygu Selcen, Andrew G Engel (2010). "Myofibrillar Myopathy."
  • Forrest, K. M., et.al. (2011). "Infantile onset myofibrillar myopathy due to recessive CRYAB mutations." Neuromuscul Disord 21(1): 37-40. PubMed ID: 21130652
  • Inagaki, N., et.al. (2006). "Alpha B-crystallin mutation in dilated cardiomyopathy." Biochem Biophys Res Commun 342(2): 379-86. PubMed ID: 16483541
  • Liu, Y., et.al. (2006). "A novel alphaB-crystallin mutation associated with autosomal dominant congenital lamellar cataract." Invest Ophthalmol Vis Sci 47(3): 1069-75. PubMed ID: 16505043
  • Sacconi et al. A novel CRYAB mutation resulting in multisystemic disease. Neuromuscul Disord. 22(1):66-72, 2012. PubMed ID: 21920752
  • Selcen D, Ohno K, Engel AG. 2004. Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patients. Brain 127(Pt 2): 439-451. PubMed ID: 14711882
  • Vicart, P., et.al. (1998). "A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy." Nat Genet 20(1): 92-5. PubMed ID: 9731540

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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