Laron Syndrome/Pituitary Dwarfism II (Growth Hormone Insensitivity) via the GHR 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
9917 GHR 81405 81405,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9917GHR81405 81405, 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

Short stature is a multifactorial developmental disorder. Laron syndrome (also known as pituitary dwarfism II or growth hormone insensitivity; OMIM 262500) is a genetic disorder of postnatal growth failure due to defective growth hormone receptor (GHR). Laron syndrome patients fail to generate insulin-like growth factor 1 (IGF1), which is important for signal transduction pathways required for growth (Laron. J Clin Endocrinol Metab 89:1031-1044, 2004; Amselem et al. J Clin Invest 87:1098-1102, 1991). Laron syndrome is characterized by severe short stature, severe growth retardation, delayed bone age, truncal obesity, severe hypoglycemia, blue sclerae, hip degeneration, and characteristic facies with frontal bossing. Additional biochemical findings include a normal to high serum growth hormone level and a low level of serum IGF-I and its binding protein 3 (IGFBP-3) (Laron 2004; Amselem et al. 1991; Berg et al. Am J Hum Genet 52:998-1005, 1993; Pantel et al. J Clin Endocrinol Metab 88:1705-1710, 2003). Of note, Laron syndrome patients do not response to exogenous growth hormone treatment (Laron 2004; Berg et al. 1993).

Genetics

Laron syndrome is an autosomal recessive disorder caused by variants in the GHR gene; however dominant negative variants leading to skipping of exon 9 have been reported in two different families (Godowski et al. Proc. Nat. Acad. Sci. 86:8083-8087, 1989; Ayling et al. Nat Genet 16:13-14, 1997; Lida et al. J Clin Endocrinol Metab 83:531-537, 1998). The GHR gene encodes a growth hormone receptor (GHR), which consists of an extracellular domain that generates the soluble growth hormone binding protein (GHBP), a short transmembrane domain and a cytoplasmic domain required for signal transduction. The GHR receptor dimerizes upon binding to the growth hormone to activate an intracellular signal transduction pathway that leads to the synthesis and secretion of insulin-like growth factor 1 (Laron 2004, Huang et al. Mol Endicrinol 18:1471-1485, 2004). A mix of missense, nonsense, splicing, frameshift, and gross deletion variants within the GHR gene has been reported (Laron 2004, Amselem et al. 1991, Berg et al. 1993; Pantel et al. 2003; David et al. J Clin Endocr Metab 92: 655-659, 2007; David et al. Eur J Endocrinol 162:37-42, 2010).

Clinical Sensitivity - Sequencing with CNV PGxome

Sensitivity of this test is currently unknown.

Testing Strategy

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

Candidates for this test are patients with symptoms consistent with Laron syndrome and family members of patients who have known GHR variants. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GHR.

Gene

Official Gene Symbol OMIM ID
GHR 600946
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Amselem, S., et.al. (1991). "Recurrent nonsense mutations in the growth hormone receptor from patients with Laron dwarfism." J Clin Invest 87(3): 1098-102. PubMed ID: 1999489
  • Amselem, S., et.al. (1991). "Recurrent nonsense mutations in the growth hormone receptor from patients with Laron dwarfism." J Clin Invest 87(3): 1098-102. PubMed ID: 1999489
  • Ayling, R. M., et.al. (1997). "A dominant-negative mutation of the growth hormone receptor causes familial short stature." Nat Genet 16(1): 13-4. PubMed ID: 9140387
  • Berg, M. A., et.al. (1993). "Diverse growth hormone receptor gene mutations in Laron syndrome." Am J Hum Genet 52(5): 998-1005. PubMed ID: 8488849
  • Berg, M. A., et.al. (1993). "Diverse growth hormone receptor gene mutations in Laron syndrome." Am J Hum Genet 52(5): 998-1005. PubMed ID: 8488849
  • David, A., et.al. (2007). "An intronic growth hormone receptor mutation causing activation of a pseudoexon is associated with a broad spectrum of growth hormone insensitivity phenotypes." J Clin Endocrinol Metab 92(2): 655-9. PubMed ID: 17148568
  • David, A., et.al. (2010). "Identification and characterisation of a novel GHR defect disrupting the polypyrimidine tract and resulting in GH insensitivity." Eur J Endocrinol 162(1): 37-42. PubMed ID: 19812236
  • Godowski, P. J., et.al. (1989). "Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism." Proc Natl Acad Sci U S A 86(20): 8083-7. PubMed ID: 2813379
  • Huang, Y., et.al. (2004). "Physical and functional interaction of growth hormone and insulin-like growth factor-I signaling elements." Mol Endocrinol 18(6): 1471-85. PubMed ID: 15044591
  • Iida, K., et.al. (1998). "Growth hormone (GH) insensitivity syndrome with high serum GH-binding protein levels caused by a heterozygous splice site mutation of the GH receptor gene producing a lack of intracellular domain." J Clin Endocrinol Metab 83(2): 531-7. PubMed ID: 9467570
  • Laron, Z. (2004). "Laron syndrome (primary growth hormone resistance or insensitivity): the personal experience 1958-2003." J Clin Endocrinol Metab 89(3): 1031-44. PubMed ID: 15001582
  • Laron, Z. (2004). "Laron syndrome (primary growth hormone resistance or insensitivity): the personal experience 1958-2003." J Clin Endocrinol Metab 89(3): 1031-44. PubMed ID: 15001582
  • Pantel, J., et.al. (2003). "Heterozygous nonsense mutation in exon 3 of the growth hormone receptor (GHR) in severe GH insensitivity (Laron syndrome) and the issue of the origin and function of the GHRd3 isoform." J Clin Endocrinol Metab 88(4): 1705-10. PubMed ID: 12679461
  • Pantel, J., et.al. (2003). "Heterozygous nonsense mutation in exon 3 of the growth hormone receptor (GHR) in severe GH insensitivity (Laron syndrome) and the issue of the origin and function of the GHRd3 isoform." J Clin Endocrinol Metab 88(4): 1705-10. PubMed ID: 12679461

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

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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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