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Smith-Lemli-Opitz Syndrome via the DHCR7 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
9573 DHCR7 81405 81405,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9573DHCR781405 81405,81479 $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.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

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

For Sanger Sequencing click here.

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

  • McKenna Kyriss, PhD

Clinical Features and Genetics

Clinical Features

Smith-Lemli-Opitz syndrome (SLOS) (OMIM 270400) is a deficiency in the enzyme 7-dehydrocholesterol reductase, which catalyzes the last step in the biosynthesis of cholesterol. Affected children have high plasma 7-dehydrocholesterol/cholesterol ratios. The enzyme deficiency leads to a variety of developmental problems including growth and mental retardation, 2-3 toe syndactyly, microcephaly, anteverted nares, ptosis, genital abnormalities, heart defects, polydactyly, and photosensitivity. The most severe cases are usually diagnosed in infancy, with milder cases diagnosed in childhood or even adult life. The great majority of SLOS patients have some clinical features of autism (Sikora et al. Am J Med Genet A 140A:1511-1518, 2006).

Genetics

Smith-Lemli-Opitz syndrome (SLOS) exhibits autosomal recessive inheritance. Variants in the DHCR7 gene encoding 7-dehydrocholesterol reductase are the only known cause of SLOS. About 130 causative DHCR7 variants have been reported to date (Witsch- Baumgartner et al. Hum Mut 17:172-182, 2001; Correa-Cerro and Porter. Mol Genet Metab 84:112-126, 2005). About 90% of these variants are missense, although “gene knockout” variants (splicing, nonsense, and frameshift) are also known. Among those with European ancestry, the most common variants appear to be c.964-1G>C (IVS8-1G>C), p.Thr93Met, p.Trp151*, p.Arg404Cys, and p.Val326Leu. Carrier rates for SLOS in some populations may be as high as 1/30. Missed diagnoses and especially spontaneous miscarriages may explain the difference between the expected incidence based on carrier rates and the actual incidence of roughly 1/30,000 (Nowaczyk et al. Am J Med Genet A 140A:2057-62, 2006).

Clinical Sensitivity - Sequencing with CNV PGxome

Using DNA sequencing and characterizing patients by plasma sterol concentrations and clinical features, Witsch-Baumgartner et al. (2000) detected two likely causative variants in 78 out of 84 (93%) SLOS patients and one likely causative variant in the remaining 6 (7%).

Testing Strategy

This test provides full coverage of all coding exons of the DHCR7 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. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

All patients with biochemical and clinical features of SLOS are candidates for this test. We will also sequence the DHCR7 gene in relatives of patients to determine carrier status. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in DHCR7.

Gene

Official Gene Symbol OMIM ID
DHCR7 602858
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Smith-Lemli-Opitz Syndrome AR 270400

Related Test

Name
Pelger-Huet Anomaly and Greenberg Skeletal Dysplasia via the LBR Gene

Citations

  • Correa-Cerro, L. S., Porter, F. D. (2005). "3beta-hydroxysterol Delta7-reductase and the Smith-Lemli-Opitz syndrome." Mol Genet Metab 84(2): 112-26. PubMed ID: 15670717
  • Nowaczyk, M. J., et.al. (2006). "DHCR7 mutation carrier rates and prevalence of the RSH/Smith-Lemli-Opitz syndrome: where are the patients?." Am J Med Genet A 140(19): 2057-62. PubMed ID: 16906538
  • Sikora, D. M., et.al. (2006). "The near universal presence of autism spectrum disorders in children with Smith-Lemli-Opitz syndrome." Am J Med Genet A 140(14): 1511-8. PubMed ID: 16761297
  • Witsch-Baumgartner, M., et.al. (2000). "Mutational spectrum in the Delta7-sterol reductase gene and genotype-phenotype correlation in 84 patients with Smith-Lemli-Opitz syndrome." Am J Hum Genet 66(2): 402-12. PubMed ID: 10677299
  • Witsch-Baumgartner, M., et.al. (2001). "Frequency gradients of DHCR7 mutations in patients with Smith-Lemli-Opitz syndrome in Europe: evidence for different origins of common mutations." Eur J Hum Genet 9(1): 45-50. PubMed ID: 11175299

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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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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