DNA icon

Restrictive Dermopathy and Mandibuloacral Dysplasia with Type B Lipodystrophy via the ZMPSTE24 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
8495 ZMPSTE24 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8495ZMPSTE2481479 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

Restrictive dermopathy (RD; OMIM 275210) is a rare disorder observed in newborns that is characterized by tight, translucent and rigid skin, joint contractures and distinctive craniofacial abnormalities including the hallmark “O” shaped mouth and micrognathia. Newborns with RD rarely live beyond the first week of life. Mandibuloacral dysplasia with type B lipodystrophy (MADB; OMIM 608612) is a progeroid syndrome characterized by mandibular and clavicular hypoplasia, joint contractures, delayed closure of the cranial sutures, atrophic skin, and lipodystrophy. In addition to these typical findings, one case of ZMPTE24-associated MADB was found with a complex presentation including congenital myopathy with fiber type disproportion (Ben Yaou et al. Eur J Hum Genet 19:647-654, 2011). This patient was found to be homozygous for a novel ZMPSTE24 missense variant. A severe presentation of MADB was reported in Japanese siblings who were compound heterozygous for an inactivating nonsense variant and a missense variant (Miyoshi et al. Clin Genet 73: 535–544, 2008).

Genetics

Restrictive dermopathy and mandibuloacral dysplasia may be caused by variant in the ZMPSTE24 gene or less often by variants in the LMNA gene. ZMPSTE24-associated RD and MADB are inherited in an autosomal recessive manner (Navarro et al. Hum Molec Genet 14:1503-1513, 2005; Agarwal et al. Hum Molec Genet 12:1995-2001, 2003). LMNA-associated RD is inherited in an autosomal dominant manner (Navarro et al. Hum Molec Genet 13:2493-2503, 2004), while LMNA-associated mandibuloacral dysplasia with type A lipodystrophy is inherited in an autosomal recessive manner (Novelli et al. Am J Hum Genet 71:426-431, 2002). ZMPSTE24 is located on chromosome 1p34 and encodes a zinc metalloendoproteinase that is involved in processing farnesylated prelamin A to mature lamin A. Consequently, inactivating variants in the ZMPSTE24 gene lead to loss of expression of lamin A and abnormal patterns of nuclear morphology and mislocalization of lamin-associated proteins (Navarro et al. Hum Molec Genet 13:2493-2503, 2004). The c.1085dupT variant is the most common ZMPSTE24 variant associated with RD and is thought to originate from a European founder (Miner Am J Med Genet 152A:2140–2141). Inactivating variants (nonsense, frame-shift, splice site) are the most common type of variant in the ZMPSTE24 gene.

Clinical Sensitivity - Sequencing with CNV PGxome

The prevalence of these disorders is too low to estimate clinical sensitivity. Analytical sensitivity should be high as nearly all ZMPSTE24 variants reported to date are expected to be detected by gene sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the ZMPSTE24 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

Clinical presentations consistent with RD or MADB. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ZMPSTE24.

Gene

Official Gene Symbol OMIM ID
ZMPSTE24 606480
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Agarwal, A. K., et.al. (2003). "Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia." Hum Mol Genet 12(16): 1995-2001. PubMed ID: 12913070
  • Ben Yaou, R., et.al. (2011). "Type B mandibuloacral dysplasia with congenital myopathy due to homozygous ZMPSTE24 missense mutation." Eur J Hum Genet 19(6): 647-54. PubMed ID: 21267004
  • Miner, J. H. (2010). "Restrictive dermopathy and ZMPSTE24 mutations in Mennonites: Evidence for allelic heterogeneity." Am J Med Genet A 152A(8): 2140-1; author reply 2142. PubMed ID: 20635340
  • Miyoshi, Y., et.al. (2008). "Severe mandibuloacral dysplasia caused by novel compound heterozygous ZMPSTE24 mutations in two Japanese siblings." Clin Genet 73(6): 535-44. PubMed ID: 18435794
  • 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
  • Navarro, C. L., et.al. (2005). "Loss of ZMPSTE24 (FACE-1) causes autosomal recessive restrictive dermopathy and accumulation of Lamin A precursors." Hum Mol Genet 14(11): 1503-13. PubMed ID: 15843403
  • Novelli, G., et.al. (2002). "Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C." Am J Hum Genet 71(2): 426-31. PubMed ID: 12075506

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

loading Loading... ×

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.
Total Price: $
×
Copy Text to Clipboard
×