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Cortical Dysplasia, Complex, with Other Brain Malformations 3 via the KIF2A 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
4257 KIF2A 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4257KIF2A81479 81479,81479 $890 Order Options and Pricing

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).

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

  • Li Fan, MD, PhD, FCCMG, FACMG

Clinical Features and Genetics

Clinical Features

KIF2A-related cortical dysplasia, complex, with other brain malformations 3 is a rare neurological disorder with onset as early as a few months old. The major symptoms include lissencephaly and microcephaly (variable congenital and postnatal microcephaly, up to −5 SD), seizures, spastic tetraplegia, and delayed psychomotor development. The minor features include intrauterine growth retardation, hypotonia, mild dysmorphic facial features, and nystagmus. MRI image analysis shows pachygyria, agyria, thick cortex, subcortical band heterotopia, thin corpus callosum, and more (Cavallin et al. 2017. PubMed ID: 27747449).  

As cortical dysplasia can be caused by defects in many genes with variable and overlapping presentations, it is difficult to diagnose by clinical manifestation and image studies only. An accurate molecular diagnosis is critical for treatment, prognosis, and prediction of recurrence risk as well as future family planning.

Genetics

KIF2A-related cortical dysplasia, complex, with other brain malformation 3 is inherited in an autosomal dominant manner. Pathogenic variants in KIF2A include missense and nonsense. A large deletion has also been reported in the KIF2A locus (Human Gene Mutation Database). De novo variants are common in this disorder (Cavallin et al. 2017. PubMed ID: 27747449).

KIF2A encodes kinesin heavy chain member 2A, which is from the kinesin-13 family, implicated in the regulation of microtubule plus-end dynamics. KIF2A protein is expressed in the developing cerebral cortex. The proteins in the kinesin superfamily play important roles in neuronal function and development via interactions with microtubules (Homma et al. 2003. PubMed ID: 12887924). Functional studies revealed that pathogenic variants in the KIF2A alter cortical neuronal positioning, change neural progenitor proliferation, impair mitotic spindle integrity and mitotic progression, and lead to defects of interneuron migration (Broix et al. 2018. PubMed ID: 29077851). A conditional knock-in mouse model with a heterozygous KIF2A: p.His321Asp had malformations of cortical development. Neuroanatomical anomalies and microcephaly associated with abnormal behavior and susceptibility to seizures were observed in the model, which correlates with the human phenotype (Gilet et al. 2020. PubMed ID: 31919497). KIF2A is relative intolerant to missense and loss-of-function variants (Genome Aggregation Database). Overall, KIF2A has been cited as a non-essential gene for growth of human tissue culture cells (Online Gene Essentiality).

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in KIF2A are a rare causes of cortical dysplasia. In 162 patients with cortical dysplasia, two cases had a pathogenic variant in KIF2A (Poirier et al. 2013. PubMed ID: 23603762).

Testing Strategy

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

This test provides full coverage of all coding exons of the KIF2A 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

KIF2A sequencing is recommended for patients who are suspected to have cortical dysplasia. Targeted testing is indicated for family members of patients who have a known pathogenic variant in KIF2A.

Gene

Official Gene Symbol OMIM ID
KIF2A 602591
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Broix et al. 2018. PubMed ID: 29077851
  • Cavallin et al. 2017. PubMed ID: 27747449
  • Genome Aggregation Database (gnomAD).
  • Gilet et al. 2020. PubMed ID: 31919497
  • Homma et al. 2003. PubMed ID: 12887924
  • Human Gene Mutation Database (Biobase).
  • Online GEne EssentialityDatabase (OGEE).
  • Poirier et al. 2013. PubMed ID: 23603762

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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