Cornelia de Lange Syndrome via the HDAC8 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
15245 HDAC8 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15245HDAC881479 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.

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

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 mutations in NIPBL, SMC1A, SMC3, RAD21 and HDAC8. HDAC8-related Cornelia de Lange syndrome (OMIM#300882) is inherited in an X-linked manner. Female carriers may show symptoms depending on X-inactivation (Mannini, L. et al. Hum Mutat Aug 29, 2013. [Epub ahead of print]). HDAC8 protein (Histone deacetylase 8 protein) coded by HDAC8, is an enzyme in the histone deacetylase family and plays a key role in transcriptional regulation by affecting the acetylation state of core histones in the nucleus of cells. It is also involved in the deacetylation of cohesin complex protein SMC3, regulating release of cohesin complexes from chromatin (Buggy, J.J. et al. Biochem J 350(1):199-205, 2000; Deardorff, M.A. et al. Nature 489(7415):313-317, 2012). To date, five mutations (four missense, 1 nonsense) have been found in patients with Cornelia de Lange syndrome and a splicing mutation has been found in a large Dutch family with intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual facial features. Some of these features overlap with Wilson-Turner syndrome (OMIM#309585) (Harakalova, M. et al. J Med Genet 49(8): 539-543, 2012).

Clinical Sensitivity - Sequencing with CNV PG-Select

One study identified HDAC8 mutations in five out of 154 individuals affected with CdLS syndrome without NIPBL mutations (Deardorff, M.A. et al. Nature 489(7415):313-317, 2012).

Testing Strategy

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

This test provides full coverage of all coding exons of the HDAC8 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.

Indications for Test

Candidates for this test are patients with symptoms consistent with Cornelia de Lange Syndrome, particularly with a family pattern consistent with X-linked inheritance, and the family members of patients who have known HDAC8 mutations.

Gene

Official Gene Symbol OMIM ID
HDAC8 300269
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Cornelia de Lange syndrome 5 XL 300882
Wilson-Turner syndrome XL 309585

Citations

  • Buggy, J.J. et al. (2000). "Cloning and characterization of a novel human histone deacetylase, HDAC8" Biochem J 350 Pt 1:199-205. PubMed ID: 10926844
  • Deardorff MA, Bando M, Nakato R, Watrin E, Itoh T, Minamino M, Saitoh K, Komata M, Katou Y, Clark D, Cole KE, Baere E De, et al. 2012. HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle. Nature 489: 313–317. PubMed ID: 22885700
  • Deardorff, M.A. et al.  2011. Cornelia de Lange Syndrome. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301283
  • Harakalova, M. et al. (2012). “X-exome sequencing identifies a HDAC8 variant in a large pedigree with X-linked intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual face.”  J Med Genet 49(8): 539-543. PubMed ID: 22889856
  • Mannini L, Cucco F, Quarantotti V, Krantz ID, Musio A. 2013. Mutation Spectrum and Genotype-Phenotype Correlation in Cornelia de Lange Syndrome. Human Mutation 34: 1589–1596. PubMed ID: 24038889

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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