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Cornelia de Lange Syndrome via the ANKRD11 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
9915 ANKRD11 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9915ANKRD1181479 81479,81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

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

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. 2012). KBG syndrome is characterized by macrodontia of central upper incisors, mental retardation, dysmorphic facial features, short statue, skeletal anomalies and global developmental delay, seizures, and intellectual disability. KBG syndrome clinically overlaps with Cornelia de Lange syndrome (Ockeloen et al. 2015; Parenti et al. 2016). Cornelia de Lange syndrome is caused by pathogenic variants in 8 genes: NIPBL, SMC3, RAD21, SMC1A, HDAC8, KMT2A, AFF4, and ANKRD11.

Genetics

ANKRD11-related CdLS and KBG syndrome are inherited in an autosomal dominant manner. The ANKRD11 protein belongs to the family of ankyrin repeat-containing cofactors that interacts with histone deacetylases to regulate gene expression. Almost 50 pathogenic variants have been reported, mainly found in patients with KBG syndrome. Most of these variants are truncating caused by nonsense variants or frameshifts. Missense and splice variants are rare. Large deletions/duplications account for ~30% of reported pathogenic variants (Human Gene Mutation Database). Only 4 unique, pathogenic variants were reported in patients affected with CdLS, all de novo, truncating variants (Ansari et al. 2014; Parenti et al. 2016).

Clinical Sensitivity - Sequencing with CNV PG-Select

Clinical sensitivity is high for patients with KGB syndrome. For example, in one study, sequencing analysis identified an ANKRD11 pathogenic variant in 12 out of 13 studied KGB families (Ockeloen et al. 2015). ANKRD11 pathogenic variants were only identified in a few CdLS patients who did not have pathogenic variants in NIPBL, SMC1A, SMC3, HDAC8 and RAD21 (Ansari et al. 2014; Parenti et al. 2016).

Large deletions/duplications account for ~30% of reported variants in ANKRD11 (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the ANKRD11 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with symptoms consistent with KBG syndrome and the family members of patients who have known ANKRD11 pathogenic variants. Patients with clinical presentations similar to Cornelia de Lange syndrome, who have no pathogenic variants in other Cornelia de Lange syndrome related genes are also candidates.

Gene

Official Gene Symbol OMIM ID
ANKRD11 611192
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
KBG Syndrome AD 148050

Related Tests

Name
Cornelia de Lange Syndrome (CdLS) Panel
Cornelia de Lange Syndrome via the SMC1A Gene

Citations

  • Ansari M. et al. 2014. Journal of Medical Genetics. 51: 659-68. PubMed ID: 25125236
  • Deardorff M.A. et al. 2012. American Journal of Human Genetics. 90: 1014-27. PubMed ID: 22633399
  • Human Gene Mutation Database (Bio-base).
  • Ockeloen C.W. et al. 2015. European Journal of Human Genetics. 23: 1270. PubMed ID: 26269249
  • Parenti I. et al. 2016. Clinical Genetics. 89: 74-81. PubMed ID: 25652421

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

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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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