Stuttering Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10143 AP4E1 81479,81479 Order Options and Pricing
GNPTAB 81479,81479
GNPTG 81479,81479
NAGPA 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10143Genes x (4)81479 81479(x8) $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our Custom Panel tool.

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

Clinical Features and Genetics

Clinical Features

Stuttering (also called stammering) is speech characterized by frequent repetition; prolongation of sounds, syllables, or words; or by frequent hesitations or pauses that disrupt the rhythmic flow of speech. Stuttering affects ~1% of the population and has a mean onset of around 30 months of age (Yairi and Ambrose. 1992. PubMed ID: 1405533). Stuttering often resolves spontaneously before adulthood, particularly in females. In rare cases, stuttering can occur in adulthood as a result of brain injury (Fawcett. 2005. PubMed ID: 15685118) or drug use (Krishnakanth et al. 2008. PubMed ID: 18787667). Secondary behaviors, such as eye blinking or other involuntary head movements, are not uncommon (Prasse and Kikano. 2008. PubMed ID: 18540491).

The advantages of genetic testing may primarily be limited to aiding in the prediction of speech therapy outcomes in the context of persistent developmental stuttering (Frigerio-Domingues et al. 2019. PubMed ID: 31003007). Patients and their families may also benefit from a molecular diagnosis for prognostic information, symptom management, and reproductive planning.

Genetics

Variants in GNPTAB, GNPTG, NAGPA, and AP4E1 have been associated with stuttering (Kang et al. 2010. PubMed ID: 20147709; Raza et al. 2015. PubMed ID: 26544806). Nearly all variants were missense and the great majority of the patients were heterozygous for the variants, although a few homozygous individuals in consanguineous kindreds were also reported. Penetrance of the variants for non-syndromic stuttering does not appear to be complete. The contribution of de novo variants in the GNPTAB, GNPTG, NAGPA, and AP4E1 genes to the development is stuttering is not known.

GNPTAB and GNPTG variants have also been reported in patients with mucolipidosis types II and III. In contrast to stuttering, mucolipidosis appears to be a solely autosomal recessive disorder associated with different, more severe variants (Raza et al. 2016. PubMed ID: 26130485). AP4E1 variants have also been reported in patients with autosomal recessive syndromic intellectual disability due to AP4E1 deficiency (Moreno-De-Luca et al. 2011. PubMed ID: 20972249; Abou Jamra et al. 2011. PubMed ID: 21620353; Kong et al. 2013. PubMed ID: 23472171). However, patients with persistent stuttering that are heterozygous for AP4E1 variants do not appear to display any features consistent with the autosomal recessive phenotype (Raza et al. 2015. PubMed ID: 26544806).

Copy number variants spanning one or more exons have been reported in association with GNPTAB, NAGPA and AP4E1-related disorders. A heterozygous deletion encompassing the entire NAGPA gene has been reported in a patient with intellectual disability, speech problems, spastic movement disorder, and tall stature (Asadollahi et al. 2014. PubMed ID: 25106414). A homozygous deletion encompassing the entire AP4E1 gene has been reported in patients with spastic cerebral palsy (Moreno-De-Luca et al. 2011. PubMed ID: 20972249; Gambin et al. 2017. PubMed ID: 27980096). Large deletions, duplications, and insertions involving one or more exons of GNPTAB have been reported in patients with mucolipidosis (Tappino et al. 2008. PubMed ID: 17964840; Otomo et al. 2009. PubMed ID: 19197337; Velho et al. 2019. PubMed ID: 30882951). For GNPTAB, GNPTG, NAGPA, and AP4E1, the contribution of gross deletions, duplications, and/or insertions to stuttering is not clear at this time.

The GNPTABGNPTG, and NAGPA genes encode enzymes involved in the lysosomal enzyme-targeting pathway. The AP4E1 gene encodes a protein involved in protein-sorting at the trans-Golgi network that physically interacts with the NAGPA enzyme.

See individual gene summaries for more information about molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

Approximately 8-16% of patients with persistent stuttering have variants in GNPTAB, GNPTG, and NAGPA (Raza et al. 2016. PubMed ID: 26130485). Variants in AP4E1 may underlie an additional ~2-4% of cases of persistent stuttering (Raza et al. 2015. PubMed ID: 26544806).

Testing Strategy

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

This panel provides 100% coverage of all coding exons of the genes 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 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

All stuttering patients are candidates for this test, although it is expected that test yield will be higher for patients with a family history of stuttering or speech characterized by more than 4% stuttering dysfluencies, as measured by instruments such as the Stuttering Severity Instrument, 3rd Edition (Kang et al. 2010. PubMed ID: 20147709; Riley. 1972. PubMed ID: 5057250).

Genes

Official Gene Symbol OMIM ID
AP4E1 607244
GNPTAB 607840
GNPTG 607838
NAGPA 607985
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
PGxome®
Mucolipidosis and Stuttering via the GNPTAB Gene
Mucolipidosis and Stuttering via the GNPTG Gene
Spastic Paraplegia 51 via the AP4E1 Gene
Stuttering via the NAGPA Gene

Citations

  • Abou Jamra et al. 2011. PubMed ID: 21620353
  • Asadollahi et al. 2014. PubMed ID: 25106414
  • Fawcett. 2005. PubMed ID: 15685118
  • Frigerio-Domingues et al. 2019. PubMed ID: 31003007
  • Gambin et al. 2017. PubMed ID: 27980096
  • Kang et al. 2010. PubMed ID: 20147709
  • Kong et al. 2013. PubMed ID: 23472171
  • Krishnakanth et al. 2008. PubMed ID: 18787667
  • Moreno-De-Luca et al. 2011. PubMed ID: 20972249
  • Otomo et al. 2009. PubMed ID: 19197337
  • Prasse and Kikano. 2008. PubMed ID: 18540491
  • Raza et al. 2015. PubMed ID: 26544806
  • Raza et al. 2016. PubMed ID: 26130485
  • Riley. 1972. PubMed ID: 5057250
  • Tappino et al. 2008. PubMed ID: 17964840
  • Velho et al. 2019. PubMed ID: 30882951
  • Yairi and Ambrose. 1992. PubMed ID: 1405533

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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