Primary Microcephaly, Autosomal Recessive, via the STIL 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
8059 STIL 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8059STIL81479 81479(x2) $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

  • Renee Bend, PhD

Clinical Features and Genetics

Clinical Features

Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder that results from hypoplasia of the cerebral cortex. The hallmark clinical feature of MCPH is head circumference at least three standard deviations below the population mean for age and sex (Jackson et al. Am J Hum Genet 63:541-546, 1998; Passemard et al. GeneReviews, 2009, www.genetests.org). In MCPH patients, microcephaly is usually detectable by the 32nd week of gestation and is apparent at birth (Woods et al. Am J Hum Genet 76:717-728, 2005). Typically, microcephaly persists throughout the patient’s lifetime. Additional features often include a sloping forehead, various degrees of cognitive disabilities, seizures, congenital hearing loss, and short stature. Brain imaging findings may include reduction of the cerebral cortical volume with simplification of the gyral cortical pattern, pachygyria with cortical thickening, lissencephaly, and polymicrogyria (Jackson et al. Am J Hum Genet 71:136-142, 2002; Passemard et al. Neurology 73:962-969, 2009; Nicholas et al. Nat Genet 42:1010-1014, 2010; Yu et al. Nat Genet 42:1015-1020, 2010; Bacino et al. Am J Med Genet A 158A:622-625, 2012). MCPH is pan ethnic. However, its incidence is variable and ranges from 1 in 30,000 to 1 in 250,000 living births (Passemard et al. GeneReviews, 2009, www.genetests.org). Incidence is highest in populations where consanguineous marriages are broadly practiced (Bundey and Alam. Eur J Hum Genet 1:206-219, 1993).

Genetics

MCPH is a genetically heterogeneous disorder. To date, eight genes (ASPM, WDR62, MCPH1, CEP152, CENPJ, STIL, CDK5RAP2 and CEP135) have been implicated in the disorder (Bond et al. Nat Genet 32:316-320, 2002; Bilgüvar et al. Nature 467:207-210, 2010; Jackson, 2002; Guernsey et al. Am J Hum Genet 87:40-51, 2010; Bond et al. Nat Genet 37:353–355, 2005; Kumar et al. Am J Hum Genet 84:286–290, 2009; Hussain et al. Am J Hum Genet 90:871-878, 2012). STIL mutations appear to be a rare cause of MCPH. To date, only three pathogenic variants were reported in five families of Indian origin (Kumar, 2009). All mutations are predicted to result in truncated proteins and include one single nucleotide change, one splicing variant and one single nucleotide deletion. MCPH patients with STIL mutations that have been reported have reduced head circumference and various degrees of mental retardation. No other symptoms were detected (Kumar, 2009). STIL encodes the SCL/TAL1 interrupting locus, a cytosolic protein that has been involved in several cellular processes including microsomal functions (Kumar 2009).

Clinical Sensitivity - Sequencing with CNV PGxome

This test will detect mutations in less than 5% of patients with a clinical diagnosis of primary microcephaly (Passemard et al. GeneReviews, 2009, www.genetests.org).

Testing Strategy

This test provides full coverage of all coding exons of the STIL 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

Patients with head circumference at least three standard deviations below the age and sex mean, with or without central nervous system anomalies, and with a family history consistent with autosomal recessive mode of inheritance and no mutations in the ASPM or WDR62 genes (Passemard et al. GeneReviews, 2009; Bacino, 2012). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in STIL.

Gene

Official Gene Symbol OMIM ID
STIL 181590
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Primary Autosomal Recessive Microcephaly 7 AR 612703

Related Tests

Name
CENPJ-Related Disorders via the CENPJ Gene
Primary Microcephaly, Autosomal Recessive, via the CDK5RAP2 Gene
Primary Microcephaly, Autosomal Recessive, via the MCPH1 Gene
Primary Microcephaly, Autosomal Recessive, via the WDR62 Gene
Seckel Syndrome, Primary Microcephaly and Familial Cutaneous Telangiectasia and Cancer Syndrome via the ATR Gene

Citations

  • Bacino et al. 2012. PubMed ID: 22308068
  • Bilgüvar et al.  Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations.  Nature 467:207-10, 2010. PubMed ID: 20729831
  • Bond et al. ASPM is a major determinant of cerebral cortical size. Nat Genet 32:316-320, 2002. PubMed ID: 12355089
  • Bond et al. A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size. Nat Genet 37:353–355, 2005. PubMed ID: 15793586
  • Bundey and Alam.  A five-year prospective study of the health of children in different ethnic groups, with particular reference to the effect of inbreeding.  Eur J Hum Genet 1:206-219, 1993. PubMed ID: 8044647
  • Guernsey et al.  Mutations in centrosomal protein CEP152 in primary microcephaly families linked to MCPH4.  Am J Hum Genet 87:40-51, 2010. PubMed ID: 20598275
  • Hussain et al.  A truncating mutation of CEP135 causes primary microcephaly and disturbed centrosomal function.  Am J Hum Genet 90:871-878, 2012. PubMed ID: 22521416
  • Jackson et al. 1998. PubMed ID: 9683597
  • Jackson et al. Identification of microcephalin, a protein implicated in determining the size of the human brain. Am J Hum Genet 71:136–142, 2002. PubMed ID: 12046007
  • Jackson et al.  Identification of microcephalin, a protein implicated in determining the size of the human brain. Am J Hum Genet 71:136–142, 2002.
  • Kumar et al. 2009. PubMed ID: 19215732
  • Nicholas et al. 2010. PubMed ID: 20890279
  • Passemard et al. Expanding the clinical and neuroradiologic phenotype of primary microcephaly due to ASPM mutations. Neurology 73:962-969, 2009. PubMed ID: 19770472
  • Passemard et al. GeneReviews, 2009
  • Verloes et al. 2013. PubMed ID: 20301772
  • Woods et al. 2005. PubMed ID: 15806441
  • Yu et al. 2010. PubMed ID: 20890278

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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