Congenital Hypothyroidism (Thyroid Dyshormonogenesis) via the SLC5A5/NIS Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 11687 | SLC5A5 | 81479 | 81479,81479 | $990 | 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 platform).
Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).
The Sanger Sequencing method for this test is NY State approved.
For Sanger Sequencing click here.Turnaround Time
3 weeks on average for standard orders or 2 weeks 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.
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
SLC5A5-related CH is an autosomal recessive disorder due to thyroid hormonogenesis defects. SLC5A5 (also known as NIS) encodes a sodium-iodide symporter (NIS). NIS transports iodine across the basolateral membrane of thyroid follicular cells and is regulated by TSH. Radioactive iodide uptake is reduced or absent in patients having biallelic SLC5A5/NIS loss of function variants (Pohlenz et al. 2000; Bizhanova et al. 2009). About 15 SLC5A5/NIS mutations are documented to date, including missense/nonsense variants, small deletions/insertions, and one complex rearrangement (Bizhanova et al. 2009; Kosugi et al. 1998; Paroder et al. 2013).
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). Pathogenic variants in SLC5A5 appear to be a rare cause of CH. About 15 SLC5A5/NIS pathogenic variants have been reported so far in a total of about 10 patients, including one complex rearrangement (Human Gene Mutation Database).
Testing Strategy
This test provides full coverage of all coding exons of the SLC5A5 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 hypothyroidism and absence of anti-thyroid antibodies. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SLC5A5.
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 SLC5A5.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| SLC5A5 | 601843 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Thyroid Dyshormonogenesis 1 | AR | 274400 |
Citations
- Bizhanova A, Kopp P. 2009. Minireview: The sodium-iodide symporter NIS and pendrin in iodide homeostasis of the thyroid. Endocrinology 150: 1084–1090. PubMed ID: 19196800
- Human Gene Mutation Database (Bio-base).
- Kosugi S, Inoue S, Matsuda A, Jhiang SM. 1998. Novel, missense and loss-of-function mutations in the sodium/iodide symporter gene causing iodide transport defect in three Japanese patients. J. Clin. Endocrinol. Metab. 83: 3373–3376. PubMed ID: 9745458
- Nettore IC, Cacace V, Fusco C De, Colao A, Macchia PE. 2013. The molecular causes of thyroid dysgenesis: a systematic review. J. Endocrinol. Invest. 36: 654–664. PubMed ID: 23698639
- Park SM, Chatterjee VKK. 2005. Genetics of congenital hypothyroidism. J. Med. Genet. 42: 379–389. PubMed ID: 15863666
- Paroder V, Nicola JP, Ginter CS, Carrasco N. 2013. The iodide-transport-defect-causing mutation R124H: a δ-amino group at position 124 is critical for maturation and trafficking of the Na+/I- symporter. J. Cell. Sci. 126: 3305–3313. PubMed ID: 23690546
- Péter F, Muzsnai A. 2011. Congenital disorders of the thyroid: hypo/hyper. Pediatr. Clin. North Am. 58: 1099–1115, ix. PubMed ID: 21981951
- Pohlenz J, Duprez L, Weiss RE, Vassart G, Refetoff S, Costagliola S. 2000. Failure of membrane targeting causes the functional defect of two mutant sodium iodide symporters. J. Clin. Endocrinol. Metab. 85: 2366–2369. PubMed ID: 10902780
- Rose SR, Brown RS, Foley T, Kaplowitz PB, Kaye CI, Sundararajan S, Varma SK, American Academy of Pediatrics; Section on Endocrinology and Committee on Genetics, American Thyroid Association; Public Health Committee, Lawson Wilkins Pediatric Endocrine Society. 2006. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics 117: 2290–2303. PubMed ID: 16740880
- Weber G, Rabbiosi S, Zamproni I, Fugazzola L. 2013. Genetic defects of hydrogen peroxide generation in the thyroid gland. J. Endocrinol. Invest. 36: 261–266. 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.
- 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
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
PGxome (Exome) Sequencing Panel
PGnome (Genome) Sequencing Panel
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ORDER OPTIONS
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2) Select Additional Test Options
No Additional Test Options are available for this test.