Primary Microcephaly, Autosomal Recessive, Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10285 ASPM 81407,81479 Order Options and Pricing
CDK5RAP2 81479,81479
CENPJ 81479,81479
CEP135 81479,81479
CEP152 81479,81479
CIT 81479,81479
KNL1 81479,81479
MCPH1 81479,81479
STIL 81479,81479
WDR62 81407,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10285Genes x (10)81479 81407, 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

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

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

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 a head circumference at least three standard deviations below the population mean for age and sex (Jackson et al. 1998. PubMed ID: 9683597). In MCPH patients, microcephaly is usually detectable by the 32nd week of gestation and is apparent at birth (Woods et al. 2005. PubMed ID: 15806441). 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. 2002. PubMed ID: 12046007; Passemard et al. 2009. PubMed ID: 19770472; Nicholas et al. 2010. PubMed ID: 20890279; Yu et al. 2010. PubMed ID: 20890278; Bacino et al. 2012. PubMed ID: 22308068). MCPH is panethnic. However, its incidence is variable and ranges from 1 in 30,000 to 1 in 250,000 living births (Komai et al. 1955. PubMed ID: 14361394; Verloes et al. 2013. PubMed ID: 20301772). Incidence is highest in populations where consanguineous marriages are broadly practiced (Bundey and Alam. 1993. PubMed ID: 8044647).

Genetics

Autosomal recessive primary microcephaly is a genetically heterogeneous disorder. Ten genes have been implicated in the disorder: ASPM, WDR62, MCPH1, CEP152, CENPJ, STIL, CDK5RAP2, CEP135, KNL1 and CIT (Bond et al. 2002. PubMed ID: 12355089; Bilgüvar et al. 2010. PubMed ID: 20729831; Jackson et al. 2002. PubMed ID: 12046007; Guernsey et al. 2010. PubMed ID: 20598275; Bond et al. 2005. PubMed ID: 15793586; Kumar et al. 2009. PubMed ID: 19215732; Hussain et al. 2012. PubMed ID: 22521416; Li et al. 2016. PubMed ID: 27453578; Genin et al. 2012. PubMed ID: 22983954). To date, over 270 causative variants have been reported. ASPM pathogenic variants are the major cause of MCPH and account for up to 54% of cases with known pathogenic variants (Bond et al. 2003. PubMed ID: 14574646). WDR62 and MCPH1 pathogenic variants are the second most common cause (Nicholas et al. 2010. PubMed ID: 20890279). Pathogenic variants in the remaining genes appear to be rare and account for less than 5% each (Verloes et al. 2013. GeneReviews PMID: 20301772).

The vast majority of pathogenic variants are predicted to result in truncated proteins and include substitutions leading to premature stop codons, small deletions/insertions, and splicing variants. Large deletions were reported only in the MCPH1, ASPM and WDR62 genes. Although rare, missense variants and complex rearrangements have been documented. See individual gene test descriptions for information on molecular biology of gene products.

Clinical Sensitivity - Sequencing with CNV PGxome

Gene Sensitivity %
ASPM 25 to 54
WDR62 < 10
MCPH1 < 10
CENPJ < 5
STIL < 5
CDK5RAP2 < 5
CEP152 < 5
CEP135 < 5
KNL1 < 5
CIT Only three families reported to date*

Sensitivity corresponds to the percentage of all cases with known disease-causing variants (Verloes et al. 2013. PMID: 20301772).

*Li et al. 2016. PubMed ID: 27453578

Pathogenic large copy number variations have been reported only in three genes included in this panel: MCPH1, ASPM, and WDR62.

MCPH1 deletions were identified in about 3% of patients with autosomal recessive primary microcephaly (Darvish et al. 2010. PubMed ID: 20978018). To date, only one and two large deletions have been reported in the WDR62 and ASPM genes, respectively (Wang et al. 2017. PubMed ID: 27784895; Nicholas et al. 2009. PubMed ID: 19028728; Passemard et al. 2009. PubMed ID: 19770472).

Testing Strategy

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

This panel typically provides 99.5% coverage of all coding exons of the genes 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 coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

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 (Bacino et al. 2012. PubMed ID: 22308068).

Genes

Official Gene Symbol OMIM ID
ASPM 605481
CDK5RAP2 608201
CENPJ 609279
CEP135 611423
CEP152 613529
CIT 605629
KNL1 609173
MCPH1 607117
STIL 181590
WDR62 613583
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

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

View Ordering Instructions

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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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