Cornelia de Lange Syndrome via the SMC1A Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 4821 | SMC1A | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
Turnaround Time
3 weeks on average for standard orders or 2 weeks 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.
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. Variants in SMC1A account for ~5% of CdLS (Deardorff et al. 2011). SMC1A-related CdLS (OMIM #300590) is inherited in an X-linked dominant manner. SMC1A encodes structural maintenance of chromosomes protein 1A, which is the human homolog of the yeast Smc1 gene, a core component of the cohesin complex forming a heterodimer with Smc3. SMC1A, although residing on chromosome Xp11.22, has been reported to escape X-chromosome inactivation (Brown et al. Hum Mol Genet 4:251–255, 1995). The majority of variants in SMC1A are missense and frameshift variants, although gross deletions and duplications as well as chromosomal rearrangement has been documented in rare cases with CdLS (Yan et al. J Med Genet 46:626-634, 2009; Hoppman-Chaney et al. Am J Med Genet 158A:193-198,2012; DeScipio et al. Am J Med Genet 137A:276–282, 2005).
Clinical Sensitivity - Sequencing with CNV PG-Select
This test is predicted to detect disease variants in ~5% of individuals with clinical features of CdLS (Musio et al. Nat Genet. 38:528–530, 2006; Borck et al. Hum Mutat 28:205–206, 2007, Deardorff et al. Am J Hum Genet 80:485–494, 2007).
Testing Strategy
This test provides full coverage of all coding exons of the SMC1A 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 clinical features consistent with Cornelia de Lange syndrome but who tested negative for NIPBL and family members of patients who have known SMC1A variants.
Candidates for this test are patients with clinical features consistent with Cornelia de Lange syndrome but who tested negative for NIPBL and family members of patients who have known SMC1A variants.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| SMC1A | 300040 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Cornelia de Lange syndrome 2 | XL | 300590 |
Related Tests
| Name |
|---|
| Cornelia de Lange Syndrome (CdLS) Panel |
| Cornelia de Lange Syndrome via the ANKRD11 Gene |
| Facial Dysostosis Related Disorders Panel |
Citations
- Borck et al. Hum Mutat 28:205–206, 2007 PubMed ID: 17221863
- Brown et al. Hum Mol Genet 4:251–255, 1995 PubMed ID: 7757075
- 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
- DeScipio et al. Am J Med Genet 137A:276–282, 2005 PubMed ID: 16075459
- Musio A, Selicorni A, Focarelli ML, Gervasini C, Milani D, Russo S, Vezzoni P, Larizza L. 2006. X-linked Cornelia de Lange syndrome owing to SMC1L1 mutations. Nature Genetics 38: 528–530. PubMed ID: 16604071
- Yan et al. J Med Genet 46:626-634, 2009 PubMed ID: 19052029
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
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
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ORDER OPTIONS
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2) Select Additional Test Options
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