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Congenital Hypothyroidism (Thyroid Hormone Resistance) via the THRA 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
11743 THRA 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11743THRA81479 81479,81479 $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

  • Greg Fischer, PhD

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 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 mild form of THR, isolated biochemical abnormalities can be the only findings. A defect in the thyroid hormone receptor beta gene (THRB) accounts for almost 85% of THR cases (Dumitrescu et al. 2013; Ferrara et al. 2012; Amor et al. 2014). Heterozygous pathogenic variants in the thyroid hormone receptor alpha gene (THRA) lead to a rare form of THR with mild congenital hypothyroidism as a predominant clinical presentation. So far, about 10 patients from eight families were identified to harbor a THRA pathogenic variant. Common clinical features include elevated serum T3:T4 ratio, mild growth retardation, mild skeletal dysplasia, and constipation (Mullem et al. 2014; Bochukova et al. 2012; Tylki-Szymanska et al. 2015).

Genetics

THRA-associated disorder is an autosomal dominant disorder. The THRA gene encodes a thyroid hormone nuclear receptor and functions as a ligand-dependent transcription factor. The mutant protein inhibits the function of the wild-type receptor in a dominant negative manner. So far, documented THRA pathogenic variants are missense and nonsense variants, and small deletion/insertions (Mullem et al. 2014; Bochukova et al. 2012; Tylki-Szymanska et al. 2015).

Clinical Sensitivity - Sequencing with CNV PGxome

Over 85% of cases of thyroid hormone resistance (THR) are caused by THRB pathogenic variants. THRA pathogenic variants are a rare cause of THR. So far, about 10 patients from eight families were identified to harbor a THRA pathogenic variant (Mullem et al. 2014; Tylki-Szymanska et al, 2015). No gross deletion and duplication variants affecting the THRA gene have been reported so far.

Testing Strategy

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

Individuals with clinical symptoms consistent with thyroid hormone resistance and absence of anti-thyroid antibodies.

Gene

Official Gene Symbol OMIM ID
THRA 190120
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Hypothyroidism, Congenital, Nongoitrous, 6 AD 614450

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
  • Bochukova E, Schoenmakers N, Agostini M, Schoenmakers E, Rajanayagam O, Keogh JM, Henning E, Reinemund J, Gevers E, Sarri M, Downes K, Offiah A, Albanese A, Halsall D, Schwabe JW, Bain M, Lindley K, Muntoni F, Vargha-Khadem F, Dattani M, Farooqi IS, Gurnell M, Chatterjee K. 2012. A mutation in the thyroid hormone receptor alpha gene. N. Engl. J. Med. 366: 243–249. PubMed ID: 22168587
  • 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
  • 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
  • Tylki-Szymanska A, Acuna-Hidalgo R, Krajewska-Walasek M, Lecka-Ambroziak A, Steehouwer M, Gilissen C, Brunner HG, Jurecka A, Rózdzynska-Swiatkowska A, Hoischen A, Chrzanowska KH. 2015. Thyroid hormone resistance syndrome due to mutations in the thyroid hormone receptor α gene (THRA). J. Med. Genet. 52: 312–316. PubMed ID: 25670821

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.
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