Laminopathies via the LMNA 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
12037 LMNA 81406 81406,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
12037LMNA81406 81406, 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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Lamin A/C (LMNA) codes for isoforms A and C of the protein lamin, a structural component of the nuclear membrane. Mutations in LMNA are known to cause at least 8 distinct clinical disorders (Genschel and Schmidt. Hum Mut 16:451-459, 2000).

Disorder Name OMIM ID
Charcot-Marie-Tooth disease type 2B1, recessive (CMT2B1) 605588
Dilated cardiomyopathy, dominant (CMD1A) 115200
Dunnigan-type familial partial lipodystrophy, dominant (FPLD2) 151660
Emery-Dreifuss muscular dystrophy, dominant (EMD2D2) 181350
Emery-Dreifuss muscular dystrophy, recessive (EDMD3) 604929
Hutchinson-Gilford progeria syndrome, de novo (HGPS) 176670
Limb-girdle muscular dystrophy type 1B, dominant (LGMD1B) 159001
Restrictive dermopathy, recessive (RD) 275210

Genetics

With the exceptions of EDMD3, CMT2B1 and RD, the laminopathies are inherited as autosomal dominant or de novo conditions. Mutations are distributed throughout the gene and, although all types of changes have been reported, the vast majority cause amino acid substitutions.

Sequencing of exon 11 of the LMNA gene, revealed that 18 out of 20 classical cases of HGPS harbored an identical de novo single-base substitution, c.1824 C>T (p.Gly608Gly) (Eriksson et al., Nature 423: 293-298, 2003). One additional de novo case was identified with a c.1822G>A substitution (p.Gly608Ser) within the same codon. Both of these mutations result in activation of a cryptic splice site within exon 11, resulting in production of a protein product that deletes 50 amino acids near the carboxy terminus.

Clinical Sensitivity - Sequencing with CNV PGxome

Diagnosis of some laminopathies is complicated by genetic heterogeneity. Thus, a negative LMNA sequencing test may not rule-out a diagnosis of these disorders when classic clinical findings are present. In cases of RD, evaluation of the ZMPSTE24 gene is also indicated (Navarro et al. Hum Mol Genet 13:2493-2503, 2004). Evaluation of muscle biopsy, if available, is a reasonable diagnostic approach to patients with symptoms suggesting muscle pathology.

Testing Strategy

This test provides full coverage of all coding exons of the LMNA 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Suspected diagnosis of any of the laminopathies.

Suspected Hutchinson-Gilford Progeria Syndrome. ***Given the rarity and severity of this condition, PreventionGenetics feels that it is important that all physicians ordering this testing for HGPS or other progeroid syndromes contact the Progeria Research Foundation (http://www.progeriaresearch.org/) for the latest information on treatment, research and patient support.***

This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in LMNA.

Gene

Official Gene Symbol OMIM ID
LMNA 150330
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Eriksson, M., et.al. (2003). "Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome." Nature 423(6937): 293-8. PubMed ID: 12714972
  • Genschel J, Schmidt HH. 2000. Mutations in the LMNA gene encoding lamin A/C. Hum. Mutat. 16: 451–459. PubMed ID: 11102973
  • Navarro, C. L., et.al. (2004). "Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy." Hum Mol Genet 13(20): 2493-503. PubMed ID: 15317753

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.

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

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ORDER OPTIONS

View Ordering Instructions

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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.

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