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Symphalangism, Proximal, Multiple Synostoses Syndrome, Stapes Ankylosis with Broad Thumb and Toes, Tarsal-Carpal Coalition Syndrome, and Brachydactyly, Type B2 via the NOG 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
9219 NOG 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9219NOG81479 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.

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

  • Juan Dong, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Symphalangism, proximal (SYNS1, also called Cushing symphalangism) is characterized by joint fusion mainly at the proximal interphalangeal joints of hands and feet, and carpal bone malformation. The major problems of this condition are tarsal bone coalition and conductive hearing loss due to fusion of the stapes to the petrous part of the temporal bone (Gong et al. 1999).

Multiple synostoses syndrome (also called facio-audio-symphalangism) is a more severe type of proximal sympalangism characterized by progressive fusion of multiple joints, conductive hearing loss and the unique feature of a broad hemicylindrical nose (Usami et al. 2012; Lee et al. 2014).

Stapes ankylosis with broad thumb and toes (also called Teunissen-Cremers syndrome) is characterized by progressive conductive hearing loss with subtle skeletal dysplasias (Brown et al. 2002).

Tarsal-carpal coalition syndrome is characterized by fusion of the carpal, tarsal and phalanges, shortening of the first metacarpal, and humeroradial fusions (Debeer et al. 2004)

Brachydactyly, type B2: Brachydactyly refers to shortening of the fingers and/or toes. The major features of Brachydactyly, type B2 are shortening of phalanges IV and V, with a milder deficiency of distal phalanges II and III (Lehmann et al. 2007).

Genetics

Pathogenic variants in NOG cause the five autosomal dominant conditions mentioned above, which show high penetrance and variable expressivity. The NOG protein (also called Noggin) is an antagonist of bone morphogenetic proteins (BMPs) in the TGF-beta superfamily and plays a key role during bone and joint formation. To date, more than 50 unique pathogenic variants have been reported. They are: missense (60%), nonsense (11%), small deletion/duplication (13%), gross deletion involving NOG (11%) and complex rearrangements (4%) (Gong et al. 1999; Debeer et al. 2004; Lehmann et al. 2007; Laurell et al. 2013, Human Gene Mutation Database). De novo pathogenic variants were seen in a few cases (Usami et al. 2012).

Clinical Sensitivity - Sequencing with CNV PGxome

This test is predicted to detect pathogenic variants in patients affected with a clinical diagnosis of Symphalangism, proximal, Multiple synostoses syndrome, Stapes ankylosis with broad thumb and toes, Tarsal-carpal coalition syndrome, and Brachydactyly, type B2. Testing of large series of patients have not been reported; therefore the clinical test sensitivities for these disorders are currently unknown.

Testing Strategy

This test provides full coverage of all coding exons of the NOG 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 NOG-related disorders and the family members of patients who have known NOG pathogenic variants.

Gene

Official Gene Symbol OMIM ID
NOG 602991
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Robinow Syndrome and Autosomal Recessive Brachydactyly, Type B1 via the ROR2 Gene

Citations

  • Brown DJ, Kim TB, Petty EM, Downs CA, Martin DM, Strouse PJ, Moroi SE, Milunsky JM, Lesperance MM. 2002. Autosomal dominant stapes ankylosis with broad thumbs and toes, hyperopia, and skeletal anomalies is caused by heterozygous nonsense and frameshift mutations in NOG, the gene encoding noggin. Am. J. Hum. Genet. 71: 618–624. PubMed ID: 12089654
  • Debeer P, Baten E, Huysmans C, Ven WJM Van de, Fryns J-P, Devriendt K. 2004. A novel NOG mutation Pro37Arg in a family with tarsal and carpal synostoses. American Journal of Medical Genetics 128A: 439–440. PubMed ID: 15264296
  • Debeer P, Baten E, Huysmans C, Ven WJM Van de, Fryns J-P, Devriendt K. 2004. A novel NOG mutation Pro37Arg in a family with tarsal and carpal synostoses. American Journal of Medical Genetics 128A: 439–440. PubMed ID: 15264296
  • Gong Y, Krakow D, Marcelino J, Wilkin D, Chitayat D, Babul-Hirji R, Hudgins L, Cremers CW, Cremers FPM, Brunner HG, Reinker K, Rimoin DL, Cohn DH, Goodman FR, Reardon W, Patton M, Francomano CA, Warman ML. 1999. Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis. Nat Genet 21: 302–304. PubMed ID: 10080184
  • Gong Y, Krakow D, Marcelino J, Wilkin D, Chitayat D, Babul-Hirji R, Hudgins L, Cremers CW, Cremers FPM, Brunner HG, Reinker K, Rimoin DL, Cohn DH, Goodman FR, Reardon W, Patton M, Francomano CA, Warman ML. 1999. Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis. Nat Genet 21: 302–304. PubMed ID: 10080184
  • Human Gene Mutation Database (Bio-base).
  • Laurell T, Lundin J, Anderlid B-M, Gorski JL, Grigelioniene G, Knight SJL, Krepischi ACV, Nordenskjöld A, Price SM, Rosenberg C, Turnpenny PD, Vianna-Morgante AM, Nordgren A. 2013. Molecular and clinical delineation of the 17q22 microdeletion phenotype. Eur J Hum Genet 21: 1085–1092. PubMed ID: 23361222
  • Lee BH, Kim O-H, Yoon H-K, Kim J-M, Park K, Yoo H-W. 2014. Variable phenotypes of multiple synostosis syndrome in patients with novel NOG mutations. Joint Bone Spine 81: 533–536. PubMed ID: 25241334
  • Lehmann K, Seemann P, Silan F, Goecke TO, Irgang S, Kjaer KW, Kjaergaard S, Mahoney MJ, Morlot S, Reissner C, Kerr B, Wilkie AOM, Mundlos S. 2007. A New Subtype of Brachydactyly Type B Caused by Point Mutations in the Bone Morphogenetic Protein Antagonist NOGGIN. Am J Hum Genet 81: 388-396. PubMed ID: 17668388
  • Lehmann K, Seemann P, Silan F, Goecke TO, Irgang S, Kjaer KW, Kjaergaard S, Mahoney MJ, Morlot S, Reissner C, Kerr B, Wilkie AOM, Mundlos S. 2007. A New Subtype of Brachydactyly Type B Caused by Point Mutations in the Bone Morphogenetic Protein Antagonist NOGGIN. Am J Hum Genet 81: 388-396. PubMed ID: 17668388
  • Usami S, Abe S, Nishio S, Sakurai Y, Kojima H, Tono T, Suzuki N. 2012. Mutations in the NOG gene are commonly found in congenital stapes ankylosis with symphalangism, but not in otosclerosis. Clinical Genetics 82: 514–520. PubMed ID: 22288654
  • Usami S, Abe S, Nishio S, Sakurai Y, Kojima H, Tono T, Suzuki N. 2012. Mutations in the NOG gene are commonly found in congenital stapes ankylosis with symphalangism, but not in otosclerosis. Clinical Genetics 82: 514–520. PubMed ID: 22288654

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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