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Autosomal Dominant Nocturnal Frontal Lobe Epilepsy via the CHRNA4 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
CHRNA4 81405 81405,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
2681CHRNA481405 81405,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

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

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

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.


Genetic Counselors


  • Eric Bend, PhD

Clinical Features and Genetics

Clinical Features

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a partial seizure disorder characterized by seizures that occur during non-REM sleep. Seizures in ADNFLE patients can present as repetitive limb movements, dystonic posturing, sleep walking, or elevation of the body or head with fear (Kurahashi and Hirose 2012). Seizures are brief, lasting from 5 seconds to 5 minutes, and often patients maintain consciousness throughout the attack. Frontal origin of ADNFLE seizures is revealed by ictal EEG recordings; interictal EEGs are normal. ADNFLE associated seizures are often managed with low doses of antiepileptic drugs (AEDs). ADNFLE is not generally associated with severe cognitive deficits or psychiatric problems, however recent evidence suggests that ADNFLE may have wider neurological phenotypes (Steinlein et al. 2012; Wood et al. 2010). It can be difficult to clinically distinguish ADNFLE from other non-epileptic paroxysmal sleep disorders, therefore a video-polysomnograph recording brain/eye/muscle activity during sleep is considered essential for diagnosis.


ADNFLE is inherited in an autosomal dominant manner and can be caused by missense mutations in the CHRNA4 or CHRNB2 genes. The S280F and S284L substitutions in CHRNA4 have been reported in ADNFLE patients of multiple ethnicities (Hwang et al. 2011). Mutations in either CHRNA4 or CHRNB2 produce indistinguishable ADNFLE phenotypes (McLellan et al. 2003).

CHRNA4 encodes a neuronally expressed subunit of the nicotinic acetylcholine receptor (nAChR). The nAChRs belong to a super-family of ligand-gated ion channels. Of the ADNFLE-associated CHRNA4 mutations reported, all are missense mutations and most are within the transmembrane domains of the receptor. Highly conserved residues within the transmembrane domain dictate the ligand-specificity and activity of the receptor. Reported mutations in CHRNA4 are gain of function, resulting in an increased sensitivity of neuronal nAChRs to the agonist acetylcholine (Phillips et al. 2001). It is hypothesized that increased nAchR activity underlies the epilepsy phenotype associated with CHRNA4 mutations.

Clinical Sensitivity - Sequencing with CNV PG-Select

Mutations in CHRNA4 were identified in 1 of 21 (~5%) of families with ADNFLE and 1 in 33 (~3%) of individuals with sporadic NFLE (Chen et al. 2009; Rozycka et al. 2003).

Testing Strategy

This test provides full coverage of all coding exons of the CHRNA4 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for CHRNA4 sequencing include patients with nocturnal seizures or individuals with a family history of ADNFLE.


Official Gene Symbol OMIM ID
CHRNA4 118504
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Epilepsy, Nocturnal Frontal Lobe, Type 1 AD 600513

Related Test

Autosomal Dominant Nocturnal Frontal Lobe Epilepsy via the CHRNB2 Gene


  • Chen Y, Wu L, Fang Y, He Z, Peng B, Shen Y, Xu Q. 2009. A novel mutation of the nicotinic acetylcholine receptor gene CHRNA4 in sporadic nocturnal frontal lobe epilepsy. Epilepsy Research 83: 152–156. PubMed ID: 19058950
  • Hwang S-K, Makita Y, Kurahashi H, Cho Y-W, Hirose S. 2011. Autosomal dominant nocturnal frontal lobe epilepsy: a genotypic comparative study of Japanese and Korean families carrying the CHRNA4 Ser284Leu mutation. J. Hum. Genet. 56: 609–612. PubMed ID: 21753767
  • Kurahashi H, Hirose S. 2012. Autosomal Dominant Nocturnal Frontal Lobe Epilepsy. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301348
  • McLellan A, Phillips HA, Rittey C, Kirkpatrick M, Mulley JC, Goudie D, Stephenson JBP, Tolmie J, Scheffer IE, Berkovic SF, Zuberi SM. 2003. Phenotypic comparison of two Scottish families with mutations in different genes causing autosomal dominant nocturnal frontal lobe epilepsy. Epilepsia 44: 613–617. PubMed ID: 12681012
  • Phillips HA, Favre I, Kirkpatrick M, Zuberi SM, Goudie D, Heron SE, Scheffer IE, Sutherland GR, Berkovic SF, Bertrand D. 2001. CHRNB2 Is the Second Acetylcholine Receptor Subunit Associated with Autosomal Dominant Nocturnal Frontal Lobe Epilepsy. The American Journal of Human Genetics 68: 225–231. PubMed ID: 11104662
  • Rozycka A, Skorupska E, Kostyrko A, Trzeciak WH. 2003. Evidence for S284L mutation of the CHRNA4 in a white family with autosomal dominant nocturnal frontal lobe epilepsy. Epilepsia 44: 1113–1117. PubMed ID: 12887446
  • Steinlein, O.K. et al. (2012). "Mutations in familial nocturnal frontal lobe epilepsy might be associated with distinct neurological phenotypes." Seizure 21(2):118:123. PubMed ID: 22036597
  • Wood AG, Saling MM, Fedi M, Berkovic SF, Scheffer IE, Benjamin C, Reutens DC. 2010. Neuropsychological function in patients with a single gene mutation associated with autosomal dominant nocturnal frontal lobe epilepsy. Epilepsy & Behavior 17: 531–535. PubMed ID: 20189461


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

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