Mucolipidosis and Stuttering via the GNPTG 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
7687 GNPTG 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7687GNPTG81479 81479(x2) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

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

  • Jana Paderova, PhD

Clinical Features and Genetics

Clinical Features

Mucolipidosis III gamma (ML III γ) (OMIM 252605), also called pseudo-Hurler polydystrophy, is part of the lysosomal storage disease family. The disease manifests clinically in childhood. Phenotypic characteristics include moderate dysostosis multiplex, joint stiffness (in the shoulders, hips, and fingers), coarsening of facial features, genu valgum, restrictive lung disease, thickening and insufficiency of the mitral and aortic valves, left ventricular hypertrophy, and in a few cases, mild cognitive impairment (Raas-Rothschild and Spiegel GeneReviews 2012, www.genereviews.org). ML III γ is distinguished from Mucolipidosis III alpha/beta (ML III α/β) by a milder phenotype and by the underling causative variants.

Stuttering (also called stammering) is speech that is characterized by frequent repetition or 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 around 30 months of age (Yairi et al. J Speech Hear Res 35:782-788, 1992). Stuttering often resolves spontaneously before adulthood, particularly in females. In rare cases stuttering can occur in adulthood as a result of brain injury (Fawcett. CNS Spectrums 10:94-95, 2005) or drug use (Krishnakanth et al. Prim Care Companion J Clin Psychiatry 10:333-334, 2008). Secondary behaviors, such as eye blinking or other involuntary head movements, are not uncommon (Prasee and Kikano. Am Fam Physician 77:1271-1276, 2008).

Genetics

ML III γ is inherited in an autosomal recessive manner and is caused by variants in GNPTG (encoding the protein N-acetylglucosamine-1-phosphotransferase subunit gamma) (Raas-Rothschild et al. J Clin Invest 105:673-681, 2000). Missense, nonsense, and frameshift variants as well as small intragenic insertions and deletions have been reported as disease causing (eg Persichetti et al. Hum Mutat 30:978-84, 2009).

Variants in GNPTG, located on chromosome 16, have been associated with stuttering (Kang et al. N Engl J Med 362:677-685, 2010). GNPTG encodes the γ subunit of GlcNAc-phosphotransferase, a protein involved in the lysosomal enzyme-targeting pathway. Three heterozygous GNPTG variants were reported in stuttering patients: two missense and one in-frame duplication of three amino acids. Penetrance of the variants does not appear to be complete. Variants in the GNPTAB and NAGPA genes, also involved in the lysosomal enzyme-targeting pathway, were similarly reported in stuttering patients. PreventionGenetics offers testing of all three genes.

Clinical Sensitivity - Sequencing with CNV PG-Select

The sensitivity for the GNPTG sequencing test is >95% for ML III γ.Kang et al. 2010 reported that 25 of 393 stuttering patients (6%) had variants in one of the three genes (GNPTAB, GNPTG, and NAGPA). Four of the 25 patients had variants in GNPTG.

Testing Strategy

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

Indications for Test

For ML III γ, patients are candidates for this test if they have a family history of ML III γ, phenotypic symptoms common to ML III γ, and show increased hydrolase (β-D-hexosaminidase, β-D-glucuronidase, β-D-galactosidase, and α-D-mannosidase) activity.

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 (Riley Stuttering Severity Instrument for Children and Adults. 3rd ed. Los Angeles: Western Psychological Services 1980).

This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GNPTG.

Gene

Official Gene Symbol OMIM ID
GNPTG 607838
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Fawcett, R. G. (2005). "Stroke-associated acquired stuttering." CNS Spectr 10(2): 94-5. PubMed ID: 15685118
  • Glyndon D. Riley (1980). "Stuttering Severity Instrument for Children and Adults.".
  • Kang, C., et.al. (2010). "Mutations in the lysosomal enzyme-targeting pathway and persistent stuttering." N Engl J Med 362(8): 677-85. PubMed ID: 20147709
  • Krishnakanth, M., et.al. (2008). "Clozapine-induced stuttering: a case series." Prim Care Companion J Clin Psychiatry 10(4): 333-4. PubMed ID: 18787667
  • Persichetti, E., et.al. (2009). "Identification and molecular characterization of six novel mutations in the UDP-N-acetylglucosamine-1-phosphotransferase gamma subunit (GNPTG) gene in patients with mucolipidosis III gamma." Hum Mutat 30(6): 978-84. PubMed ID: 19370764
  • Prasse, J. E., Kikano, G. E. (2008). "Stuttering: an overview." Am Fam Physician 77(9): 1271-6. PubMed ID: 18540491
  • Raas-Rothschild, A., et.al. (2000). "Molecular basis of variant pseudo-hurler polydystrophy (mucolipidosis IIIC)." J Clin Invest 105(5): 673-81. PubMed ID: 10712439
  • Yairi, E., Ambrose, N. (1992). "Onset of stuttering in preschool children: selected factors." J Speech Hear Res 35(4): 782-8. 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

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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.
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