Cornelia de Lange Syndrome via the NIPBL 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
11515 NIPBL 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11515NIPBL81479 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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Classic Cornelia de Lange syndrome (CdLS) is characterized by distinctive facial features, growth retardation, hirsutism, and upper limb reduction defects that range from subtle phalangeal abnormalities to oligodactyly. Craniofacial features include synophrys; arched eyebrows; long eyelashes; small, upturned nose; small, widely spaced teeth; and microcephaly. IQ ranges from below 30 to 102 (mean: 53). Many individuals demonstrate autistic and self-destructive tendencies. Frequent findings include cardiac septal defects, gastrointestinal dysfunction, hearing loss, myopia, and cryptorchidism or hypoplastic genitalia. Individuals with a milder phenotype have less severe growth, cognitive, and limb involvement but often have facial features consistent with CdLS (Deardorff et al. GeneReview 2011).

Genetics

CdLS can be caused by variants in NIPBL, SMC1A, and SMC3. NIPBL-related CdLS (OMIM#122470) is inherited in an autosomal dominant manner. Variants in this gene account for about 60% of CdLS (Gillis et al. Am J Hum Genet 75:610-623, 2004). NIPBL encodes Nipped-B-like protein, which plays a role in sister chromatid cohesion and in regulating long-range enhancer-promoter interactions, possibly through interactions with the cohesin complex (Dorsett Curr Biol 14:R834-836, 2004). The majority of affected individuals have a de novo NIPBL variant; fewer than 1% of individuals with NIPBL-related CdLS have an affected parent. It has been suggested that milder forms of CdLS are more likely to be caused by missense variants and more severe forms by truncating variants (Gillis et al. 2004).

Clinical Sensitivity - Sequencing with CNV PGxome

This test is predicted to detect disease variants in ~60% of individuals with clinical features of CdLS (Gillis et al. 2004; Deardorff et al. 2011).

Testing Strategy

This test provides full coverage of all coding exons of the NIPBL 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.

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

Candidates for this test are patients with clinical features consistent with Cornelia de Lange syndrome and family members of patients who have known NIPBL variants.

Gene

Official Gene Symbol OMIM ID
NIPBL 608667
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Cornelia de Lange syndrome 1 AD 122470

Citations

  • Deardorff MA, Kaur M, Yaeger D, Rampuria A, Korolev S, Pie J, Gil-Rodríguez C, Arnedo M, Loeys B, Kline AD, Wilson M, Lillquist K, Siu V, Ramos FJ, Musio A, Jackson LS, Dorsett D, Krantz ID. 2007. Mutations in Cohesin Complex Members SMC3 and SMC1A Cause a Mild Variant of Cornelia de Lange Syndrome with Predominant Mental Retardation. The American Journal of Human Genetics 80: 485–494. PubMed ID: 17273969
  • Dorsett Curr Biol 14:R834-836, 2004 PubMed ID: 15458660
  • Gillis et al. Am J Hum Genet 75:610-623, 2004 PubMed ID: 15318302

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

loading Loading... ×

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.

Total Price: $
×
Copy Text to Clipboard
×