Short Rib Skeletal Dysplasia Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10347 DYNC2H1 81479,81479 Order Options and Pricing
DYNC2I1 81479,81479
DYNC2I2 81479,81479
EVC 81479,81479
EVC2 81479,81479
FGFR2 81479,81479
FGFR3 81479,81479
IFT122 81479,81479
IFT140 81479,81479
IFT172 81479,81479
IFT80 81479,81479
NEK1 81479,81479
PAPSS2 81479,81479
SLC26A2 81479,81479
SOX9 81479,81479
TCTN3 81479,81479
TTC21B 81479,81479
WDR19 81479,81479
WDR35 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10347Genes x (19)81479 81479 $990 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Clinical Features and Genetics

Clinical Features

Short rib-polydactyly syndrome (SRTD) is a group of skeletal ciliopathies characterized by markedly short ribs, short limbs, with or without polydactyly. Some patients may also present abnormalities involving the brain, eyes, heart, kidneys, liver, pancreas, intestines, and genitalia. SRTD includes Ellis-van Creveld syndrome, Jeune syndrome (asphyxiating thoracic dystrophy), and Mainzer-Saldino syndrome. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (Huber and Cormier-Daire 2012).

This Short Rib Skeletal Dysplasia NextGen Panel focuses on, but is not limited to the following conditions: Short-rib thoracic dysplasia, Short-rib thoracic dysplasia with or without polydactyly types, Ellis-van Creveld syndrome, Cranioectodermal dysplasia, asphyxiating thoracic dystrophy, Mainzer-Saldino syndrome, Verma-Naumoff, Brachyolmia 4 with mild epiphyseal and metaphyseal changes, diastrophic dysplasia, atelosteogenesis type II, achondrogenesis type IB, campomelic dysplasia, Pfeiffer syndrome type 3 and thanatophoric dysplasia.

Genetics

This test analyzes 19 genes involved in Short Rib Skeletal Dysplasia.

16 out of the 19 genes are related to Autosomal Recessive conditions: DYNC2H1, EVC, EVC2, IFT122, IFT140, IFT172, IFT80, NEK1, PAPSS2, SLC26A2, TCTN3, TTC21B, WDR19, DYNC2I2/WDR34, WDR35, and DYNC2I1/WDR60.

EVC and EVC2: Ellis-van Creveld syndrome, Weyers acrodental dysostosis

IFT122: Cranioectodermal dysplasia 1 (also called Sensenbrenner syndrome)

IFT80: Short-rib thoracic dysplasia 2 with or without polydactyly (also called Jeune syndrome)

DYNC2H1: Short-rib thoracic dysplasia 3 with or without polydactyly

TTC21B: Short-rib thoracic dysplasia 4 with or without polydactyly

WDR19: Short-rib thoracic dysplasia 5 with or without polydactyly, Senior-Loken syndrome 8, Cranioectodermal dysplasia

NEK1: Short-rib thoracic dysplasia 6 with or without polydactyly

WDR35: Short-rib thoracic dysplasia 7 with or without polydactyly, Cranioectodermal dysplasia 2

DYNC2I1/WDR60: Short-rib thoracic dysplasia 8 with or without polydactyly

IFT140: Short-rib thoracic dysplasia 9 with or without polydactyly (also called Mainzer-Saldino syndrome, Majewski type)

IFT172: Short-rib thoracic dysplasia 10 with or without polydactyly

DYNC2I2/WDR34: Short-rib thoracic dysplasia 11 with or without polydactyly

PAPSS2: Brachyolmia 4 with mild epiphyseal and metaphyseal changes (also called spondyloepimetaphyseal and premature pubarche)

SLC26A2: Diastrophic dysplasia broad bone-platyspondylic variant, Achondrogenesis Ib, Atelosteogenesis II (also called De la Chapelle dysplasia)

TCTN3: Joubert syndrome 18, Orofaciodigital syndrome IV

Three out of the 19 genes are related to Autosomal Dominant conditions: FGFR2, FGFR3 and SOX9.

FGFR2: Pfeiffer syndrome type 3

FGFR3: Thanatophoric dysplasia, type I and Thanatophoric dysplasia, type II

SOX9: Campomelic dysplasia, Acampomelic campomelic dysplasia

NOTE: FGFR3 pathogenic variants can also cause autosomal recessive Camptodactyly, Tall Stature, Scoliosis, and Hearing Loss Syndrome (also called CATSHL syndrome).

See individual gene test descriptions for information on clinical features and molecular biology of gene products.

Clinical Sensitivity - Sequencing with CNV PGxome

Genes tested in this panel have been implicated in Short Rib Skeletal Dysplasia and although individually these genes may be involved in a minority of Short Rib Skeletal Dysplasia, the combination of pathogenic variants may be responsible for a significant portion of Short Rib Skeletal Dysplasia.

In one study, DYNC2H1 pathogenic variants were identified in 19 out of 57 (33%) of studied families with a clinical diagnosis of asphyxiating thoracic dystrophy (Schmidts et al. 2013).

Combining EVC and EVC2, this test is predicted to detect pathogenic variants in at least two thirds of affected individuals with EVC (Tompson et al. 2007; Valencia et al. 2009). In one study, EVC and EVC2 pathogenic variants were found in 74% (20/27) and 26% (7/27) of EVC patients, respectively (D'Asdia et al. 2013).

SOX9 pathogenic variants were identified in 7 out of 9 campomelic dysplasia patients (Mattos et al. 2015).

SLC26A2 pathogenic variants were identified in >95% of individuals affected with Achondrogenesis type 1B (Rossi & Superti-Furga. 2001).

Analytical sensitivity for FGFR2 should be high, because almost 97% of known pathogenic variants are missense, splicing site and small deletions/insertions (Human Gene Mutation Database).

FGFR3 pathogenic variants were found in >99% of patients with Achondroplasia, Thanatophoric dysplasia and Muenke syndrome (Karczeski and Cutting 2013).

9 gross deletions/duplications and three complex rearrangements have been reported in EVC (D'Ambrosio et al. 2015, HGMD). Five gross deletions have been reported in EVC2 (Valencia et al. 2009; HGMD).

Only five documented pathogenic FGFR2 variants are large deletions/insertions (HGMD; Bochukova et al. 2009).

Only one large deletion was reported in the WDR35 gene (Mill et al. 2011).

To date, no gross deletions or duplications have been reported in FGFR3, ITF122, and SLC26A2 (HGMD).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 98.8% coverage of all coding exons of the genes 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 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

Individuals with a clinical presentation of Short Rib Skeletal Dysplasia or a family history of Short Rib Skeletal Dysplasia.

Genes

Official Gene Symbol OMIM ID
DYNC2H1 603297
DYNC2I1 615462
DYNC2I2 613363
EVC 604831
EVC2 607261
FGFR2 176943
FGFR3 134934
IFT122 606045
IFT140 614620
IFT172 607386
IFT80 611177
NEK1 604588
PAPSS2 603005
SLC26A2 606718
SOX9 608160
TCTN3 613847
TTC21B 612014
WDR19 608151
WDR35 613602
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Bochukova E.G. et al. 2009. Human Mutation. 30: 204-11. PubMed ID: 21473986
  • D'Ambrosio V. et al. 2015. Prenatal Diagnosis. 35: 97-9. PubMed ID: 25174843
  • D'Asdia M.C. et al. 2013. European Journal of Medical Genetics. 56: 80-7. PubMed ID: 23220543
  • Huber C, Cormier-Daire V. 2012. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics 160C: 165-174. PubMed ID: 22791528
  • Human Gene Mutation Database (Bio-base).
  • Karczeski B., Cutting G.R. 2013. Thanatophoric Dysplasia. 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: 20301540
  • Mattos E.P. et al. 2015. Genetics and Molecular Biology. 38: 14-20. PubMed ID: 25983619
  • Mill P. et al. 2011. American Journal of Human Genetics. 88: 508-15.
  • Rossi A., Superti-Furga A. 2001. Human Mutation. 17: 159-71. PubMed ID: 11241838
  • Schmidts M. et al. 2013. Journal of Medical Genetics. 50: 309-23. PubMed ID: 23456818
  • Tompson S.W. et al. 2007. Human Genetics. 120: 663-70. PubMed ID: 17024374
  • Valencia M. et al. 2009. Human Mutation. 30: 1667-75. PubMed ID: 19810119

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

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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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