Myofibrillar Myopathy via the CRYAB Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
362 CRYAB$440.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

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

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 CRYAB$990.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 20 days.

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 trichome, 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 4 months of age (Forrest et al. Neuromuscul Disord 21, 37-40 2011) with death by 3 years of age (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).


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 mutations is inherited as an autosomal recessive disorder and all cases reported thus far have had truncating mutations. The c.60delC mutation is considered a founder mutation among Canadian aboriginals of Cree descent (Del Bigio et al. 2011). A small number of CRYAB missense, nonsense, and small deletion mutations have been reported in patients with MFM (Selcen and Engel, GeneReviews 2010). Other genes involved with MFM include DES, MYOT, FLNC, LDB3, and BAG3.

Testing Strategy

The alpha-B-crystallin protein is coded by exons 1 - 3 of the CRYAB gene on chromosome 11q23. Testing is accomplished by amplifying each coding exon and ~10 bp of adjacent noncoding sequence, then determining the nucleotide sequence using standard dideoxy sequencing methods and a capillary electrophoresis instrument. We will also sequence any single exon (Test #100) in family members of patients with a known mutation or to confirm research results.

Indications for Test

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


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


Name Inheritance OMIM ID
Alpha-B Crystallinopathy 608810

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Genetic Counselors
  • Berry, V., (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., (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., (2011). "Infantile onset myofibrillar myopathy due to recessive CRYAB mutations." Neuromuscul Disord 21(1): 37-40. PubMed ID: 21130652
  • Inagaki, N., (2006). "Alpha B-crystallin mutation in dilated cardiomyopathy." Biochem Biophys Res Commun 342(2): 379-86. PubMed ID: 16483541
  • Liu, Y., (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., (1998). "A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy." Nat Genet 20(1): 92-5. PubMed ID: 9731540
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

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Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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