X-Linked Lissencephaly-1 and Subcortical Band Heterotopia via the DCX 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
8727 DCX 81405 81405,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8727DCX81405 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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Lissencephalies and subcortical band heterotopia (SBH) are a group of cerebral malformations due to an arrest of neuronal migration during embryogenesis. Lissencephaly is characterized by simplification or absence of the brain convolutions, resulting in a smooth appearance. SBH, also known as double cortex, is characterized by abnormal bands of neurons beneath a normal cortex. Lissencephalies and SBH are characterized by intellectual disability and seizures. Additional features include microcephaly, subtle dysmorphic features, failure to thrive, difficulty feeding and swallowing, malformations of the digits, muscle spasms, myoclonic jerks, cognitive impairment, and poor social interactions (Leventer et al. 2001. PubMed ID: 11502906; Wallerstein et al. 2008. PubMed ID: 18462864; Dobyns. 2010. PubMed ID: 20331703; Di Donato et al. 2017. PubMed ID: 28440899). The incidence of lissencephalies is ~1:100,000 live births (https://www.orpha.net).

Lissencephalies are clinically and genetically heterogeneous. Several forms are recognized. They are distinguished on the basis of the clinical features and the causative genes.

Lissencephaly X-linked 1 can be distinguished by MRI findings consistent with an anterior greater than posterior gradient of lissencephaly or with SBH. Neurological symptoms include developmental delay, infantile spasms, foot deformities, and variable degrees of intellectual disabilities and behavioral manifestations. The phenotype is usually more severe in male than in female patients (Pilz et al. 1998. PubMed ID: 9817918; Dobyns. 2010. PubMed ID: 20331703). SBH is more common in female compared to male patients (D'Agostino et al. 2002. PubMed ID: 12390976).

Genetics

Lissencephaly X-linked 1 and SBH are caused by pathogenic variants in the DCX gene (Ross et al. 1997. PubMed ID: 9097958; Sakamoto et al. 2000. PubMed ID: 10807542). To date, ~130 pathogenic variants have been implicated in the two forms of the disease. The majority of variants are missense. Truncating variants that include nonsense, splice site, small framsehift deletions or insertions, and large deletions have also been reported (Human Gene Mutation Database).

De novo pathogenic variants in the DCX gene have been reported in about 25% of affected male patients (Bahi-Buisson et al. 2013. PubMed ID: 23365099). Mosaicism, both somatic and germline, have been reported in ~10% of unaffected mothers (Demelas et al. 2001. PubMed ID: 11468322; D'Agostino et al. 2002. PubMed ID: 12390976; Aigner et al. 2003. PubMed ID: 12552055).

DCX encodes doublecortin, a microtubule-associated protein required for the normal migration of neurons in the cerebral cortex during brain development (Gleeson. 1998. PubMed ID: 9489700).

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in the DCX gene have been detected in about 23% of patients from a large cohort of children with lissencephaly or SBH (Di Donato et al. 2018. PubMed ID: 29671837).

Testing Strategy

This test provides full coverage of all coding exons of the DCX 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.

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

Candidates for this test are patients with X-linked lissencephaly or subcortical band heteropia (SBH), also known as double cortex.

Gene

Official Gene Symbol OMIM ID
DCX 300121
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
X-Linked Lissencephaly XL 300067

Citations

  • Aigner et al. 2003. PubMed ID: 12552055
  • Bahi-Buisson et al. 2013. PubMed ID: 23365099
  • D'Agostino et al. 2002. PubMed ID: 12390976
  • Demelas et al. 2001. PubMed ID: 11468322
  • Di Donato et al. 2018. PubMed ID: 29671837
  • Dobyns. 2010. PubMed ID: 20331703
  • Dobyns. 2010. PubMed ID: 20331703
  • Gleeson. 1998. PubMed ID: 9489700
  • Human Gene Mutation Database (Bio-base).
  • Leventer et al. 2001. PubMed ID: 11502906
  • Pilz et al. 1998. PubMed ID: 9817918
  • Ross et al. 1997. PubMed ID: 9097958
  • Sakamoto et al. 2000. PubMed ID: 10807542
  • Wallerstein et al. 2008. PubMed ID: 18462864

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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