Plectinopathy via the PLEC Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesPriceCPT Code Copy CPT Codes
593 PLEC$2420 81479 Add to Order
Targeted Testing

For ordering sequencing of 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
Clinical and analytical sensitivity cannot be estimated because these disorders are rare.

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CNV via aCGH

Test Code Test Copy GenesPriceCPT Code Copy CPT Codes
600 PLEC$990 81479 Add to Order
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Over 100

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Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Features
Plectinopathy is caused by disruption of intermediate filament crosslinking of the cytoskeleton, affecting skin and muscle (Smith et al. Nat Genet 13:450-457, 1996). Two forms of plectinopathy are known in which muscle symptoms are absent. Epidermolysis bullosa simplex with pyloric atresia (EBS-PA, OMIM 612138) is characterized by severe skin blistering at birth and congenital pyloric atresia seen by ultrasound. Affected neonates have blistering and extensive absence of skin on the face, scalp, trunk, and limbs (Morrell et al. Brit J Derm 143:1342-1343, 2000; Pfendner et al. J Invest Derm 124:111-115, 2005). Epidermolysis bullosa simplex of the Ogna type (EBS-OG, OMIM 131950) includes skin bruising in addition to the other typical skin findings. EBS-OG has been described in one family from Ogna in Norway and in one German family (Koss-Harnes et al. J Invest Derm 118:87-93, 2002). Three forms of plectinopathy occur in which muscle disease is present in combination with EBS, or as the only finding. Epidermolysis bullosa with muscular dystrophy (EBS-MD, OMIM 226670) is characterized by early childhood onset of progressive muscular dystrophy and blistering skin changes. Skin blistering may be present as early as the neonatal period and additional skin findings include atrophic scarring, nail dystrophy and alopecia. Epidermolysis bullosa simplex with congenital myasthenic syndrome (EBS-MyS) has been reported in two individuals (Banwell et al. J Neuropath Exp Neurol 58:832-846, 1999; Selcen et al. Neurol 76:327-336, 2011). Symptoms in these two cases include EBS beginning in early infancy, progressive muscle weakness, and elevated serum CK levels. Myasthenic symptoms were first present at ages 3 and 9, respectively and included progressive ocular, facial, limb, and truncal weakness, and fatigability. EMG studies demonstrated a marked decrement. Autosomal recessive limb-girdle muscular dystrophy, type 2Q (LGMD2Q, OMIM 613723) has been reported in one Turkish sibship (Gundesli et al. Am J Hum Genet 87:834-841, 2010). Muscle weakness was first noted in childhood. As a teenager, the proband exhibited the Gowers sign and lumbar lordosis. Muscle histology revealed variation in fiber size, internally placed nuclei, scattered necrotic fibers. Serum CK levels were elevated.
EBS-OG type is an autosomal dominant disorder caused by the p.Arg2110Trp mutation in the rod domain of plectin (Koss-Harnes et al. 2002).  All other forms of plectinopathy are inherited in an autosomal recessive manner.  The two reported EBS-MyS patients were African American and both were found to have the same c.12043dupG mutation in exon 32 and differing nonsense mutations in exon 31 (Selcen et al. 2011).  One mutation, a 9-bp deletion in exon 1 of isoform F, has thus far been reported to be causative for LGMD2Q (Gundesli et al. 2010).
Testing Strategy
Testing is accomplished by amplifying each coding exon (exons 1-33) and ~10 bp of adjacent noncoding sequence.  We also test exon 1 corresponding to protein isoforms B, D, and F.  Nucleotide sequence is determined 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 of plectinopathy.


Official Gene Symbol OMIM ID
PLEC 601282
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Epidermolysis Bullosa with Pyloric Atresia via the PLEC Gene


Genetic Counselors
  • Banwell et al.  J Neuropath Exp Neurol 58:832-846, 1999 PubMed ID: 10446808
  • Gundesli et al. Am J Hum Genet 87:834-841, 2010 PubMed ID: 21109228
  • Koss-Harnes et al. J Invest Derm 118:87-93, 2002 PubMed ID: 11851880
  • Morrell et al. Brit J Derm 143:1342-1343, 2000 PubMed ID: 11122061
  • Selcen et al. Neurol 76:327-336, 2011 PubMed ID: 21263134
  • Smith et al. Nat Genet 13:450-457, 1996 PubMed ID: 8696340
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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 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.

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.

In the case of duplications, aCGH will not determine the chromosomal location of the duplicated DNA. Most duplications will be tandem, but in some cases the duplicated DNA will be inserted at a different locus. This method will also not determine the orientation of the duplicated segment (direct or inverted).

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

The sensitivity of this assay is dependent upon the quality of the input DNA. In particular, highly degraded DNA will yield poor results.

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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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