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Craniosynostosis via the MSX2 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
9087 MSX2 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9087MSX281479 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

  • Stela Berisha, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Craniosynostosis is a primary abnormality of skull growth involving premature fusion of the cranial sutures causing skull deformity. MSX2 pathogenic variants cause Craniosynostosis, type 2 (also called Boston-Type Craniosynostosis), Parietal foramina 1 and Parietal foramina with cleidocranial dysplasia (Wilkie and Mavrogiannis, 2012; Florisson et al. 2013).

Genetics

MSX2-related disorders are inherited in an autosomal dominant manner. MSX2 protein coded by the MSX2 gene is a transcription factor in the homeobox family that regulates embryonic development of many organs. More than 20 unique MSX2 pathogenic variants have been reported. They are: missense (26%), small deletion/insertion (35%), large deletion/duplication (13%), and translocation/Complex rearrangements (26%) (Jabs et al. 1993; Wilkie et al. 2000; Shiihara et al. 2004; Ott et al. 2012; Mavrogiannis et al. 2006; Human Gene Mutation Database). The loss of function variant c.443C>T, p.Pro148Leu was found in patients with BOSTON-TYPE Craniosynostosis (Florisson et al. 2013). Many affected patients with Enlarged Parietal Foramina have an affected parent; the proportion of patients caused by a de novo pathogenic variant is unknown (Wilkie et al. 2012).

Clinical Sensitivity - Sequencing with CNV PGxome

MSX2 pathogenic variants can explain ~40% of patients with Enlarged Parietal Foramina (Wilkie et al. 2012).

Large deletions/duplications and translocations/Complex rearrangements account for 13% and 26% of all reported MSX2 pathogenic variants, respectively (Shiihara et al. 2004; Ott et al. 2012; Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the MSX2 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

Candidates for this test are patients with symptoms consistent with Craniosynostosis, Parietal foramina 1, Parietal foramina with cleidocranial dysplasia and the family members of patients who have known MSX2 pathogenic variants.

Gene

Official Gene Symbol OMIM ID
MSX2 123101
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
FGFR3-Related Disorders via the FGFR3 Gene
Achondroplasia via the FGFR3 Gene, Exon 10
Craniofrontonasal Syndrome via the EFNB1 Gene
Craniosynostosis and Dental Anomalies, Autosomal Recessive Crouzon-like Craniosynostosis via the IL11RA Gene
Frontonasal Dysplasia (Frontorhiny) via the ALX3 Gene
Hypochondroplasia via the FGFR3 Gene
Saethre-Chotzen Syndrome via the TWIST1 Gene
Thanatophoric Dysplasia (TD) via the FGFR3 Gene

Citations

  • Florisson JMG, Verkerk AJMH, Huigh D, Hoogeboom AJM, Swagemakers S, Kremer A, Heijsman D, Lequin MH, Mathijssen IMJ, Spek PJ van der. 2013. Boston type craniosynostosis: Report of a second mutation in MSX2. Am. J. Med. Genet. 161: 2626–2633. PubMed ID: 23949913
  • Florisson JMG, Verkerk AJMH, Huigh D, Hoogeboom AJM, Swagemakers S, Kremer A, Heijsman D, Lequin MH, Mathijssen IMJ, Spek PJ van der. 2013. Boston type craniosynostosis: Report of a second mutation in MSX2. Am. J. Med. Genet. 161: 2626–2633. PubMed ID: 23949913
  • Human Gene Mutation Database (Bio-base).
  • Human Gene Mutation Database (Bio-base).
  • Jabs EW, Müller U, Li X, Ma L, Luo W, Haworth IS, Klisak I, Sparkes R, Warman ML, Mulliken JB. 1993. A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis. Cell 75: 443–450. PubMed ID: 8106171
  • Mavrogiannis LA, Taylor IB, Davies SJ, Ramos FJ, Olivares JL, Wilkie AO. 2006. Enlarged parietal foramina caused by mutations in the homeobox genes ALX4 and MSX2: from genotype to phenotype. Eur J Hum Genet 14: 151–158. PubMed ID: 16319823
  • Ott CE, Hein H, Lohan S, Hoogeboom J, Foulds N, Grünhagen J, Stricker S, Villavicencio-Lorini P, Klopocki E, Mundlos S. 2012. Microduplications upstream of MSX2 are associated with a phenocopy of cleidocranial dysplasia. J Med Genet 49: 437–441. PubMed ID: 22717651
  • Ott CE, Hein H, Lohan S, Hoogeboom J, Foulds N, Grünhagen J, Stricker S, Villavicencio-Lorini P, Klopocki E, Mundlos S. 2012. Microduplications upstream of MSX2 are associated with a phenocopy of cleidocranial dysplasia. J Med Genet 49: 437–441. PubMed ID: 22717651
  • Shiihara T, Kato M, Kimura T, Hayasaka K, Yamamori S, Ogata T. 2004. Craniosynostosis with extra copy of MSX2 in a patient with partial 5q-trisomy. Am. J. Med. Genet. 128A: 214–216. PubMed ID: 15214020
  • Shiihara T, Kato M, Kimura T, Hayasaka K, Yamamori S, Ogata T. 2004. Craniosynostosis with extra copy of MSX2 in a patient with partial 5q-trisomy. Am. J. Med. Genet. 128A: 214–216. PubMed ID: 15214020
  • Wilkie AO, Mavrogiannis LA. 2012. Enlarged Parietal Foramina. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301307
  • Wilkie AO, Mavrogiannis LA. 2012. Enlarged Parietal Foramina. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301307
  • Wilkie AO, Mavrogiannis LA. 2012. Enlarged Parietal Foramina. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301307
  • Wilkie AOM, Tang Z, Elanko N, Walsh S, Twigg SRF, Hurst JA, Wall SA, Chrzanowska KH, Maxson RE. 2000. Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossification. Nat Genet 24: 387–390. PubMed ID: 10742103

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.
Total Price: $
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