Congenital Hypothyroidism (Thyroid Dyshormonogenesis) via the TG 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
11741 TG 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11741TG81479 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.

For Reflex to PGxome pricing click here.

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 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

Congenital hypothyroidism (CH) is the most common congenital endocrine disorder. It occurs in one of every 3,000-4,000 newborns and is twice as common in females as in males. Without early and adequate treatment, CH is characterized by growth failure, developmental delay, and permanent intellectual disability. Current newborn screening primarily detects the elevated thyroid stimulating hormone (TSH) level at birth in response to decreased or absent thyroid hormone production and can identify over 90% of CH cases. Most CH patients grow and develop normally after treatment with thyroxine (Park and Chatterjee. 2005; Rose et al. 2006).

CH is usually a sporadic disorder, but growing evidence confirms several genetic mechanisms together account for at least 5% of cases. The majority of CH cases (~80%) are due to developmental defects of the thyroid gland known as thyroid dysgenesis, including thyroid agenesis, hypoplasia, and ectopy. The remaining ~15% are caused by defects in one of the steps of thyroid hormone biosynthesis (thyroid dyshormonogenesis). Other less common causes are central hypothyroidism (impaired hypothalamic-pituitary-thyroid axis), thyroid hormone transporter defects, and thyroid hormone resistance (Péter and Muzsnai 2011; Nettore et al. 2013; Weber et al. 2013).

Genetics

TG-related CH (thyroid dyshormonogenesis) is an autosomal recessive disorder (Grasberger and Refetoff 2011). The reported incidence of TG-related CH is about 1:67,000 in the Japanese population (Hishinuma et al. 2006). TG encodes thyroglobulin, a homodimer glycoprotein, exclusively synthesized in the thyroid gland. Thyroglobulin is the non-iodine component of thyroid hormone and also the storage pool of organified iodine (Grasberger and Refetoff 2011). At least 40 patients have been reported to harbor inactivating or loss of function TG mutations. Reported TG pathogenic variants include missense, nonsense, splicing variants, small deletions/insertions, and one gross deletion (Targovnik et al. 2011; Hishinuma et al. 2000; Narumi et al. 2011).

Clinical Sensitivity - Sequencing with CNV PGxome

Congenital hypothyroidism (CH) is normally a sporadic disease, but in about 5% of cases a genetic cause has been demonstrated. Pathogenic variants in multiple genes from several molecular mechanisms are associated with CH (Péter and Muzsnai. 2011). At least 40 patients have been reported to harbor inactivating or loss of function TG mutations. In a population-based cohort of 102 patients with CH, pathogenic variants in TG were identified in five individuals (~5%) (Narumi et al. 2011). Gross deletion and duplication variants appear to be rare. A gross deletion affecting multiple exons of TG has been reported (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the TG 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

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

Gene

Official Gene Symbol OMIM ID
TG 188450
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Thyroid Dyshormonogenesis 3 AR 274700

Citations

  • Grasberger H., Refetoff S. 2011. Current Opinion in Pediatrics. 23: 421-8. PubMed ID: 21543982
  • Hishinuma A. et al. 2006. The Journal of Clinical Endocrinology and Metabolism. 91: 3100-4. PubMed ID: 16720658
  • Human Gene Mutation Database (Bio-base).
  • Narumi S. et al. 2011. The Journal of Clinical Endocrinology and Metabolism. 96: E1838-42. PubMed ID: 21900383
  • Nettore I.C. et al. 2013. Journal of Endocrinological Investigation. 36: 654-64. PubMed ID: 23698639
  • Park S.M., Chatterjee V.K. 2005. Journal of Medical Genetics. 42: 379-89. PubMed ID: 15863666
  • P├ęter F., Muzsnai A. 2011. Pediatric Clinics of North America. 58: 1099-115, ix. PubMed ID: 21981951
  • Rose S.R, American Academy of Pediatrics. et al. 2006. Pediatrics. 117: 2290-303. PubMed ID: 16740880
  • Targovnik H.M. et al. 2011. Hormone Research in Paediatrics. 75: 311-21. PubMed ID: 21372558
  • Weber G. et al. 2013. Journal of Endocrinological Investigation. 36: 261-6. PubMed ID: 23404134

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

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.

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