Thyroid Hormone Resistance via the THRB 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
15203 THRB 81405 81405,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15203THRB81405 81405, 81479 $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 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Thyroid hormone resistance (THR) is a rare genetic disorder caused by reduced tissue responsiveness to thyroid hormone. The estimated prevalence is about 1:40,000 births. The characteristic biochemical findings in patients with THR are elevated serum free thyroid hormone levels accompanied by nonsuppressed thyroid stimulating hormone production (Dumitrescu et al. 2013). The clinical presentation is highly variable and has a mixture of hypothyroidism and hyperthyroidism because of variable peripheral resistance among individuals as well as among different tissues within a single patient. Goiter is often found in 66-95% of reported cases. Symptoms related to hypothyroidism include learning disabilities, delayed growth and bone development. Hyperactivity and tachycardia are associated with high thyroid hormone levels. In the mild form of THR, isolated biochemical abnormalities may be the only findings (Dumitrescu et al. 2013; Ferrara et al. 2012; Amor et al. 2014). A defect in the thyroid hormone receptor beta gene (THRB) accounts for almost 85% of THR cases. Heterozygous mutations in the thyroid hormone receptor alpha gene (THRA) lead to a rare form of THR with congenital hypothyroidism as a predominant clinical presentation (Mullem et al. 2014).

Genetics

THRB-associated THR usually is an autosomal dominant condition secondary to dominant-negative pathogenic variants. Less commonly, it can be a recessive disorder due to loss-of-function mutations (Ferrara et al. 2012, Dumitrescu et al. 2013). De novo mutations occur in ~23% of cases, and mosaicism has been observed (Mamanasiri et al. 2012; Amor et al. 2014). The THRB gene encodes a nuclear receptor of thyroid hormone that is bound to thyroid hormone response elements of target genes and functions as a ligand-dependent transcription factor (Dumitrescu et al. 2013). Missense is the major type of documented THRB pathogenic variants. Nonsense, small deletion/insertions, and gross deletions have also been reported (Amor et al. 2014; Ferrara et al. 2012).

Clinical Sensitivity - Sequencing with CNV PG-Select

Over 85% of cases of thyroid hormone resistance (THR) are caused by THRB pathogenic variants. Gross deletions affecting multi- exons of THRB are rare and result in the recessive form of THR (Dumitrescu et al. 2013).

Testing Strategy

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

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

Indications for Test

Individuals with clinical symptoms consistent with thyroid hormone resistance and absence of anti-thyroid antibodies. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in THRB.

Gene

Official Gene Symbol OMIM ID
THRB 190160
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Amor AJ, Halperin I, Alfayate R, Borrás VM, Escribano A, González C, Gutirrez A, Mauri M, Pérez P, Picό A, Vourliotaki I, Oriola J. 2014. Identification of four novel mutations in the thyroid hormone receptor-β gene in 164 Spanish and 2 Greek patients with resistance to thyroid hormone. Hormones (Athens) 13: 74–78. PubMed ID: 24722129
  • Dumitrescu AM, Refetoff S. 2013. The syndromes of reduced sensitivity to thyroid hormone. Biochim. Biophys. Acta 1830: 3987–4003. PubMed ID: 22986150
  • Ferrara AM, Onigata K, Ercan O, Woodhead H, Weiss RE, Refetoff S. 2012. Homozygous thyroid hormone receptor β-gene mutations in resistance to thyroid hormone: three new cases and review of the literature. J. Clin. Endocrinol. Metab. 97: 1328–1336. PubMed ID: 22319036
  • Mamanasiri S, Yesil S, Dumitrescu AM, Liao X-H, Demir T, Weiss RE, Refetoff S. 2006. Mosaicism of a thyroid hormone receptor-beta gene mutation in resistance to thyroid hormone. J. Clin. Endocrinol. Metab. 91: 3471–3477. PubMed ID: 16804041
  • Mullem AA van, Visser TJ, Peeters RP. 2014. Clinical Consequences of Mutations in Thyroid Hormone Receptor-α1. Eur Thyroid J 3: 17–24. PubMed ID: 24847461

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.

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

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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.

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