Coffin-Siris Syndrome Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10221 ARID1A 81479,81479 Order Options and Pricing
ARID1B 81479,81479
DPF2 81479,81479
PHF6 81479,81479
SMARCA2 81479,81479
SMARCA4 81479,81479
SMARCB1 81479,81479
SMARCE1 81479,81479
SOX11 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10221Genes x (9)81479 81479 $1100 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

Coffin-Siris syndrome (CSS) is a multi-systemic genetic disease characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and additional digits, mild to severe developmental delay, intellectual disability, distinctive facial features, and sparse scalp hair. Other variable findings include short stature, feeding difficulties, ophthalmologic abnormalities, cardiac anomalies and hearing loss (Schrier Vergano et al. 2018. PubMed ID: 23556151; Vergano and Deardorff. 2014. PubMed ID: 25169447).

To date, ~ 200 cases of confirmed CSS have been clinically reported. The exact prevalence and incidence is not clear, but this disorder is probably underestimated. The diagnosis is generally based on the presence of major and minor clinical signs. Due to clinically heterogeneous features, CSS is sometimes misdiagnosed. Molecular genetic testing is particularly useful to reach an accurate diagnosis (Schrier Vergano et al. 2018. PubMed ID: 23556151).

Genetics

The majority of CSS is inherited in an autosomal dominant (AD) manner with high penetrance. Most patients reported to date had a de novo pathogenic variant. Pathogenic variants or genomic rearrangements in the following genes have been reported to be causative for CSS: ARID1A, ARID1B, SMARCA4, SMARCB1, SMARCE1, and SOX11 (Kosho et al. 2014. PubMed ID: 25169878; Hempel et al. 2016. PubMed ID: 26543203; Vasileiou et al. 2018. PubMed ID: 29429572. These genes encode human homologs of proteins in the BRG1- and BRM-associated factor (BAF) complex, which is also known as the mammalian switch/sucrose non-fermentable (mSWI/SNF)-like nucleosome remodeling complex. This complex is involved in the destabilization of histone-DNA interactions in an ATP-dependent manner, which is important for the expression of genes normally suppressed by chromatin (Ronan et al. 2013. PubMed ID: 23568486; Kosho and Okamoto. 2014. PubMed ID: 25168959).

In addition, a relatively few cases have been reported to be associated with single exon or partial gene deletion involving the X-linked PHF6 gene (Di Donato et al. 2014. PubMed ID: 24380767), heterozygous missense/splicing variants in DPF2 (Vasileiou et al. 2018. PubMed ID: 29429572), and several heterozygous missense variants in SMARCA2 (Santen et al. 2013. PubMed ID: 23929686).

Pathogenic variants in ARID1B are the most common cause of CSS (Wieczorek et al. 2013. PubMed ID: 23906836). ARID1A and ARID1B encode AT-rich interactive domain-containing proteins. These proteins function as alternative, mutually exclusive subunits of the SWI/SNF complex (Watanabe et al. 2014. PubMed ID: 24788099). Previous studies suggest that pathogenic variants in ARID1A and ARID1B may cause aberrant chromatin remodeling with a loss-of-function mechanism. SMARCA4, SMARCB1 and SMARCE1 belong to the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin family. The exact mechanisms of these genes in the pathology of CSS are currently not clear, but pathogenic variants in these genes may have a gain-of function or dominant-negative effect (Kosho and Okamoto. 2014. PubMed ID: 25168959). Pathogenic variants in another gene, SOX11, have also been reported to cause CSS. SOX11 is a transcription factor downstream of the BAF complex and plays an important role in neurogenesis during brain development (Tsurusaki et al. 2014. PubMed ID: 24886874; Hempel et al. 2016. PubMed ID: 26543203).

Heterozygous pathogenic variants in SMARCA4 and SMARCB1 have also been reported to cause the rhabdoid tumor predisposition syndrome (Roberts and Biegel. 2009. PubMed ID: 19305156; Hasselblatt et al. 2011. PubMed ID: 21566516; Biegel et al. 2014. PubMed ID: 25169151).

Pathogenic variants in PHF6 are mainly associated with X-linked Börjeson–Forssman–Lehmann syndrome, which is characterized by moderate to severe mental retardation, epilepsy, hypogonadism, hypometabolism, obesity with marked gynecomastia, swelling of subcutaneous tissue of the face, narrow palpebral fissure and large, but not deformed, ears (Lower et al. 2002. PubMed ID: 12415272).

Variants in SMARCA2 are mainly reported in patients with autosomal dominant Nicolaides-Baraitser syndrome characterized by sparse hair, distinctive facial morphology, distal-limb anomalies and intellectual disability, and most of these variants are de novo missense (Van Houdt et al. 2012. PubMed ID: 22366787).

Clinical Sensitivity - Sequencing with CNV PGxome

This test is expected to detect causative variants in about 60% of patients with Coffin-Siris Syndrome (Schrier Vergano et al. 2018. PubMed ID: 23556151).

Testing Strategy

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

This panel provides 100% 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 symptoms consistent with Coffin-Siris Syndrome are candidates for this test.

Genes

Official Gene Symbol OMIM ID
ARID1A 603024
ARID1B 614556
DPF2 601671
PHF6 300414
SMARCA2 600014
SMARCA4 603254
SMARCB1 601607
SMARCE1 603111
SOX11 600898
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Biegel et al. 2014. PubMed ID: 25169151
  • Di Donato et al. 2014. PubMed ID: 24380767
  • Hasselblatt et al. 2011. PubMed ID: 21566516
  • Hempel et al. 2016. PubMed ID: 26543203
  • Kosho and Okamoto. 2014. PubMed ID: 25168959
  • Kosho et al. 2014. PubMed ID: 25169878
  • Lower et al. 2002. PubMed ID: 12415272
  • Roberts and Biegel. 2009. PubMed ID: 19305156
  • Ronan et al. 2013. PubMed ID: 23568486
  • Santen et al. 2013. PubMed ID: 23929686
  • Schrier Vergano et al. 2018. PubMed ID: 23556151
  • Tsurusaki et al. 2014. PubMed ID: 24886874
  • Van Houdt et al. 2012. PubMed ID: 22366787
  • Vasileiou et al. 2018. PubMed ID: 29429572
  • Vergano and Deardorff. 2014. PubMed ID: 25169447
  • Watanabe et al. 2014. PubMed ID: 24788099
  • Wieczorek et al. 2013. PubMed ID: 23906836

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

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.

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