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Lissencephaly 1 and Subcortical Band Heteropia via the PAFAH1B1 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
9959 PAFAH1B1 81406 81406,81405 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9959PAFAH1B181406 81406,81405 $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

  • Li Fan, MD, PhD, FCCMG, FACMG

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 1 can be distinguished by MRI findings consistent with a posterior greater than anterior gradient of lissencephaly. Neurological symptoms include severe developmental delay, severe motor impairment including axial hypotonia and spastic quadripareis, no language development, autistic features, sleep disorders, postnatal microcephaly, and seizures (Saillour et al. 2009. PubMed ID: 19667223).

Genetics

Heterozygous pathogenic variants in the PAFAH1B1 gene have been implicated in lissencephaly 1 and SBH (Cardoso et al. 2000. PubMed ID: 11115846; Pilz et al. 1999. PubMed ID: 10441340). To date, ~150 pathogenic variants have been reported. The majority of variants are truncating and include nonsense, splice site, small frameshift deletions or insertions, and large copy number variants. Large pathogenic deletions are the major genetic cause of lissencephaly 1 (Human Gene Mutation Database). All pathogenic PAFAH1B1 variants have been documented to be de novo (Dobyns et al. 2014. PubMed ID: 20301752). Germline and somatic pathogenic variants have been reported (González-Morón et al. 2017. PubMed ID: 28953922; Sicca et al. 2003. PubMed ID: 14581661).

The PAFAH1B1 protein (platelet-activating factor acetylhydrolase IB alpha subunit) is required for the normal migration of neurons in the cerebral cortex during brain development (Reiner et al. 1993. PubMed ID: 8355785; Albrecht et al. 1996. PubMed ID: 8954729).

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in the PAFAH1B1 gene have been detected in about 40% 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 PAFAH1B1 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

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

Gene

Official Gene Symbol OMIM ID
PAFAH1B1 601545
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Lissencephaly 1 AD 607432

Citations

  • Albrecht et al. 1996. PubMed ID: 8954729
  • Cardoso et al. 2000. PubMed ID: 11115846
  • Di Donato et al. 2017. PubMed ID: 28440899
  • Di Donato et al. 2018. PubMed ID: 29671837
  • Dobyns et al. 2014. PubMed ID: 20301752
  • Dobyns. 2010. PubMed ID: 20331703
  • González-Morón et al. 2017. PubMed ID: 28953922
  • Human Gene Mutation Database (Bio-base).
  • Leventer et al. 2001. PubMed ID: 11502906
  • Pilz et al. 1999. PubMed ID: 10441340
  • Reiner et al. 1993. PubMed ID: 8355785
  • Saillour et al. 2009. PubMed ID: 19667223
  • Sicca et al. 2003. PubMed ID: 14581661
  • 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.
  • 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

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View Ordering Instructions

1) Select Test Method (Platform)


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.
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