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CENPJ-Related Disorders via the CENPJ 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
8089 CENPJ 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8089CENPJ81479 81479,81479 $990 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 platform).

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

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

For Sanger Sequencing click here.

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.

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 a congenital decrease of the head circumference by at least three standard deviations below the population mean for age and sex that persists throughout the patient’s lifetime. Although MCPH has been initially characterized by severe microcephaly in the absence of other congenital anomalies (Jackson et al. Am J Hum Genet 63:541-546, 1998), structural anomalies of the central nervous system have been reported in several cases (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). Additional features may include a sloping forehead, various degrees of cognitive disabilities, seizures, congenital hearing loss, and short stature. Brain imaging findings include reduction of the cerebral cortical volume without gross brain malformations with simplification of the gyral cortical pattern, pachygyria with cortical thickening, hypoplasia, lissencephaly, and polymicrogyria (Jackson et al. Am J Hum Genet 71:136-142, 2002). In MCPH patients, microcephaly is detectable by the 32nd week of gestation and is apparent at birth (Woods et al. Am J Hum Genet 76:717-728, 2005). MCPH is panethnic. However, its incidence is variable and ranges from 1 in 30,000-250,000 live births (Passemard et al. GeneReviews, 2009, www.genetests.org) and is most elevated in populations where consanguineous marriages are broadly practiced (Bundey and Alam. Eur J Hum Genet 1:206-219, 1993).

Seckel syndrome (SCKL) is a rare disorder characterized by prenatal and postnatal growth delays. Most common clinical features include low birth weight, microcephaly, proportionate short stature, and varying degrees of mental retardation. Additional features include narrow face, large eyes, beak-like protrusion of the nose, malformed ears, small jaws, clinodactyly, dysplasia of the hips, and radial dislocation (Majewski and Goecke Am J Med Genet 12:7-21, 1982).

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. Am J Hum Genet 71:136–142, 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).

CENPJ variants account for less than 5% of cases with known variants (Passemard, GeneReviews. 2009). Four variants have been reported in MCPH cases. These include two missense variants and two small deletions that are predicted to result in truncated proteins. Variants have been reported in patients from various populations.

In addition to small head and various degrees of mental retardation, MCPH patients with CENPJ variants that have been reported to date presented with facial dysmorphism, developmental delay, joint stiffness, finger deformities, and seizures (Bond 2005, Gul et al. J Hum Genet 51:760-764, 2006, Darvish J Med Genet 47:823-828, 2010).

SCKL is a genetically heterogeneous disorder that is inherited in an autosomal recessive manner. Variants in five genes (ATR, CENPJ, CEP152, PCNT, and RBBP8) have been reported to be involved in SCKL (O'Driscoll et al. Nat Genet 33:497-501, 2003; Al-Dosari et al. J Med Genet 47:411-414, 2010; Kalay et al. Nat Genet 43:23-26, 2011; Griffith et al. Nat Genet 40:232-236, 2008; Qvist et al. PLoS Genet 7(10):e1002310, Epub 2011). Most variants are expected to result in truncated proteins. To date, only one splicing variant in the CENPJ gene was reported in one consanguineous family (Al-Dosari et al. J Med Genet 47:411-414, 2010).

The CENPJ gene encodes the centromeric protein J, which is involved in several functions including the maintenance of microsome integrity and spindle morphology.

Clinical Sensitivity - Sequencing with CNV PGxome

This test will detect variants in less than 5% of patients with a clinical diagnosis of primary microcephaly (Passemard et al. GeneReviews, 2009, www.genetests.org). Variants in the CENPJ gene appear to be a rare cause of SCKL syndrome.

Testing Strategy

This test provides full coverage of all coding exons of the CENPJ 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 variants in the ASPM or WDR62 genes (Passemard et al. GeneReviews, 2009; Bacino, 2012). Patients with features suggestive of SCKL syndrome are also candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CENPJ.

Gene

Official Gene Symbol OMIM ID
CENPJ 609279
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Primary Microcephaly, Autosomal Recessive, via the CDK5RAP2 Gene
Primary Microcephaly, Autosomal Recessive, via the MCPH1 Gene
Primary Microcephaly, Autosomal Recessive, via the STIL Gene
Primary Microcephaly, Autosomal Recessive, via the WDR62 Gene

Citations

  • Al-Dosari et al. Novel CENPJ mutation causes Seckel syndrome J Med Genet 47:411-414, 2010.  PubMed ID: 20522431
  • Bacino et al. 2012. PubMed ID: 22308068
  • Bilgüvar et al. 2010. PubMed ID: 20729831
  • Bond et al. 2005. PubMed ID: 15793586
  • Bond et al. ASPM is a major determinant of cerebral cortical size. Nat Genet 32:316-320, 2002. PubMed ID: 12355089
  • Bundey and Alam. 1993. PubMed ID: 8044647
  • Darvish et al. 2010. PubMed ID: 20978018
  • Griffith et al. Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling. Nat Genet 40:232-236, 2008. PubMed ID: 18157127
  • Guernsey et al. 2010. PubMed ID: 20598275
  • Gul et al.  A novel deletion mutation in CENPJ gene in a Pakistani family with autosomal recessive primary microcephaly. J Hum Genet 51:760-764, 2006. PubMed ID: 16900296
  • Hussain et al. 2012. PubMed ID: 22521416
  • Jackson et al. 1998. PubMed ID: 9683597
  • Jackson et al. 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.
  • Kalay et al.  CEP152 is a genome maintenance protein disrupted in Seckel syndrome. Nat Genet 43:23-26, 2011. PubMed ID: 21131973
  • Kumar et al. 2009. PubMed ID: 19215732
  • Majewski and Goecke.  Studies of microcephalic primordial dwarfism I: approach to a delineation of the Seckel syndrome.  Am J Med Genet 12:7-21, 1982. PubMed ID: 7046443
  • Nicholas et al. 2010. PubMed ID: 20890279
  • O'Driscoll et al.  A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. Nat Genet 33:497-501, 2003. PubMed ID: 12640452
  • 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
  • Qvist et al.  CtIP Mutations Cause Seckel and Jawad Syndromes. PLoS Genet 7(10):e1002310, Epub 2011. PubMed ID: 21998596
  • 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

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

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View Ordering Instructions

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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.
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