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Allan-Herndon-Dudley Syndrome or Monocarboxylate Transporter 8 Deficiency via the SLC16A2 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
8515 SLC16A2 81405 81405,81404 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8515SLC16A281405 81405,81404 $890 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 backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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

Monocarboxylate transporter 8 deficiency results in Allan-Herndon-Dudley syndrome (Schwartz et al. 2005). Allan-Herndon-Dudley syndrome is characterized by infancy and childhood severe intellectual disability, hypotonia, dysarthria or absence of speech, involuntary movements, muscle hypoplasia, delay of developmental milestone, and spastic paraplegia with hyperreflexia, clonus, and Babinski reflexes. Of note, the affected males usually present disturbances in blood levels of thyroid hormones such as high free triiodothyronine T3 and low free T4 levels in serum. However, their serum TSH levels and thyroid functions are normal. The alterations in free T3 and free T4 levels provide a convenient biomarker of selecting males with intellectual disability for molecular testing in monocarboxylate transporter 8 deficiency (Müller and Heuer 2012).

Genetics

Allan-Herndon-Dudley syndrome is inherited in an X-linked recessive manner and is caused by pathogenic variants in the SLC16A2 gene encoding monocarboxylate transporter 8. Penetrance is complete, however, the severity is variable (Armour et al. 2015). Pathogenic variants in SLC16A2 include missense, nonsense, small deletion/insertion, splice site variants, and large deletions/duplications (Schwartz et al. 2005; Zung et al. 2011; Kersseboom et al. 2013; Yamamoto et al. 2013; Fischer et al. 2015).

Overall, monocarboxylate transporter 8 deficiency results in tissue-specific alterations in transportation, metabolism and targeted action of thyroid hormone. Monocarboxylate transporter 8 is highly expressed in different tissues such as liver, kidney, thyroid, pituitary and brain (Müller and Heuer 2012). The function of this transporter is to transport triiodothyronine into neurons. Thyroid hormone is essential during different stages in brain development. Loss of transporter function causes intellectual disability and leads to elevated T3 and lowered T4 levels in the blood.

Neurological involvement of Allan-Herndon-Dudley syndrome occurs predominantly in males. Manifestation in females is doubtful, but has not been studied systematically or longitudinally. Female carriers have abnormal thyroid hormone tests with no neurologic deficits (Schwartz et al 2005). The first female case with full-blown Allan-Herndon-Dudley syndrome was reported due to a de novo translocation t(X;9)(q13.2;p24) that interrupted the SLC16A2 gene. In addition, this patient's fibroblasts showed complete loss of protein expression attributed to skewed X inactivation (Frints et al. 2008).

Clinical Sensitivity - Sequencing with CNV PGxome

To date, SLC16A2 is the only gene reported to be responsible for Allan-Herndon-Dudley syndrome. Clinical sensitivity of SLC16A2 in a large cohort of patients with Allan-Herndon-Dudley syndrome relevant phenotypes is unavailable in the literature, because most of studies are case reports. Clinical sensitivity should be high in patients who meet clinical and diagnostic criteria for this disorder.

Testing Strategy

This test provides full coverage of all coding exons of the SLC16A2 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

SLC16A2 sequencing test is recommended for patients who are suspected to have Allan-Herndon-Dudley syndrome.

Gene

Official Gene Symbol OMIM ID
SLC16A2 300095
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Allan-Herndon-Dudley Syndrome XL 300523

Related Test

Name
Congenital Hypothyroidism and Thyroid Hormone Resistance Panel

Citations

  • Armour C.M. et al. 2015. Plos One. 10: e0139343. PubMed ID: 26426690
  • Fischer J. et al. 2015. Journal of Molecular Endocrinology. 54: 39-50. PubMed ID: 25527620
  • Frints S.G. et al. 2008. European Journal of Human Genetics : Ejhg. 16: 1029-37. PubMed ID: 18398436
  • Kersseboom S. et al. 2013. Molecular Endocrinology (baltimore, Md.). 27: 801-13. PubMed ID: 23550058
  • Müller J., Heuer H. 2012. European Thyroid Journal. 1: 72-9. PubMed ID: 24783000
  • Schwartz C.E. et al. 2005. American Journal of Human Genetics. 77: 41-53. PubMed ID: 15889350
  • Yamamoto S. et al. 2013. Clinical Pediatric Endocrinology : Case Reports and Clinical Investigations : Official Journal of the Japanese Society For Pediatric Endocrinology. 22: 83-6. PubMed ID: 24170966
  • Zung A. et al. 2011. European Journal of Endocrinology / European Federation of Endocrine Societies. 165: 823-30. PubMed ID: 21896621

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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