Short stature Homeobox (SHOX)-related Haploinsufficiency Disorder via the SHOX Gene
Summary and Pricing 
Test Method
Bi-Directional Sanger Sequencing
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 626 | SHOX | 81405 | 81405 | $520 | Order Options and Pricing |
Pricing Comments
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.
Turnaround Time
4 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
Short stature is a multifactorial developmental disorder. Short stature homeobox (SHOX)-related haploinsufficiency is a genetic disorder that manifests as short stature with variable clinical severity. The SHOX-related disorders include the severe Langer mesomelic dysplasia (LMD; OMIM 249700), characterized by short stature with hypoplasia/aplasia; the Leri-Weill dyschondrosteosis (LWD; OMIM 127300), characterized by disproportionate short stature with mesomelic shortening in the forearms and lower legs and bilateral Madelung deformity of the wrist; and idiopathic short stature (ISS; OMIM 300582) (Rao et al. Nat Genet 16:54-63, 1997; Shears et al. Nat Genet 19:70-73, 1998; Schiller et al. Eur J Hum Genet 8:54-62, 2000). Intrafamilial phenotypic variability has been reported with SHOX-related haploinsufficiency (Schiller et al. 2000).
Genetics
SHOX-related haploinsufficiency disorder is caused by variants in the SHOX gene (also known as SHOXY gene; Rao et al. 1997). The SHOX gene is located in the pseudoautosomal region (PAR1) on the X and Y chromosomes (Rao et al. 1997). There is a dose-dependent association between the number of active copies of the SHOX gene and height (Rappold et al. J Med Genet 44:306-313, 2007). Nullizygosity of the SHOX gene results in LMD, while haploinsufficiency of the SHOX gene results in LWD or ISS (Shears et al. 1998; Ogata et al. J Clin Endocrinol Metab 87:1390-1394, 2002; Rappold et al. 2007). Conversely, overdose of the SHOX gene is associated with tall stature (Rappold et al. 2007). The SHOX gene encodes a homeodomain transcription factor that has a role in chondrocyte proliferation and differentiation (Sabherwal et al. J Med Genet 41:e83-87, 2004). A mix of missense, nonsense, splicing, frameshift, and gross deletions and duplications variants within the SHOX gene has been reported (Rao et al. 1997; Shears et al. 1998; Schiller et al. 2000; Benito-Sanz et al. Am J Hum Genet 77:533-544, 2005; Rappold et al. 2007; Thomas et al. Am J Med Genet 149A:1407-1414, 2009).
Clinical Sensitivity - Sanger Sequencing
SHOX variants account for about 2% of idiopathic short stature cases (Schneider et al. Am J Hum Genet 77:89-96, 2005). Approximately 30% of the SHOX-related haploinsufficiency variants are point variants (Niesler et al. Hum Mut 20:338-341, 2002; Morizio et al. Am J Med Genet 119A:293-296, 2003). Gene deletions are common.
Testing Strategy
This test involves bidirectional sequencing using genomic DNA of the 5 coding exons (exons 2-6) of the SHOX gene. The full coding region of each exon plus ~10 bp of flanking non-coding DNA on each side are sequenced. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known variants or to confirm research results.
Indications for Test
Candidates for this test are patients with symptoms consistent with SHOX-related haploinsufficiency and family members of patients who have known SHOX variants.
Candidates for this test are patients with symptoms consistent with SHOX-related haploinsufficiency and family members of patients who have known SHOX variants.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| SHOX | 400020 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Langer Mesomelic Dysplasia Syndrome | 249700 | |
| Leri Weill Dyschondrosteosis | 127300 | |
| Short Stature, Idiopathic, X-Linked | 300582 |
Citations
- Benito-Sanz, S., et.al. (2005). "A novel class of Pseudoautosomal region 1 deletions downstream of SHOX is associated with Leri-Weill dyschondrosteosis." Am J Hum Genet 77(4): 533-44. PubMed ID: 16175500
- Morizono, H., et.al. (1997). "'Late onset' ornithine transcarbamylase deficiency: function of three purified recombinant mutant enzymes." Hum Mol Genet 6(6): 963-8. PubMed ID: 9175746
- Niesler, B., et.al. (2002). "The human SHOX mutation database." Hum Mutat 20(5): 338-41. PubMed ID: 12402330
- Ogata, T., et.al. (2002). "SHOX nullizygosity and haploinsufficiency in a Japanese family: implication for the development of Turner skeletal features." J Clin Endocrinol Metab 87(3): 1390-4. PubMed ID: 11889214
- Rao, E., et.al. (1997). "Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome." Nat Genet 16(1): 54-63. PubMed ID: 9140395
- Rao, E., et.al. (1997). "Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome." Nat Genet 16(1): 54-63. PubMed ID: 9140395
- Rappold, G., et.al. (2007). "Genotypes and phenotypes in children with short stature: clinical indicators of SHOX haploinsufficiency." J Med Genet 44(5): 306-13. PubMed ID: 17182655
- Sabherwal, N., et.al. (2004). "A novel point mutation A170P in the SHOX gene defines impaired nuclear translocation as a molecular cause for Leri-Weill dyschondrosteosis and Langer dysplasia." J Med Genet 41(6): e83. PubMed ID: 15173249
- Schiller, S., et.al. (2000). "Phenotypic variation and genetic heterogeneity in Leri-Weill syndrome." Eur J Hum Genet 8(1): 54-62. PubMed ID: 10713888
- Schiller, S., et.al. (2000). "Phenotypic variation and genetic heterogeneity in Leri-Weill syndrome." Eur J Hum Genet 8(1): 54-62. PubMed ID: 10713888
- Schneider, K. U., et.al. (2005). "Identification of a major recombination hotspot in patients with short stature and SHOX deficiency." Am J Hum Genet 77(1): 89-96. PubMed ID: 15931595
- Shears, D. J., et.al. (1998). "Mutation and deletion of the pseudoautosomal gene SHOX cause Leri-Weill dyschondrosteosis." Nat Genet 19(1): 70-3. PubMed ID: 9590293
- Shears, D. J., et.al. (1998). "Mutation and deletion of the pseudoautosomal gene SHOX cause Leri-Weill dyschondrosteosis." Nat Genet 19(1): 70-3. PubMed ID: 9590293
- Thomas, N. S., et.al. (2009). "Clinical and molecular characterization of duplications encompassing the human SHOX gene reveal a variable effect on stature." Am J Med Genet A 149A(7): 1407-14. PubMed ID: 19533800
Ordering/Specimens
Ordering Options
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myPrevent - Online Ordering
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Requisition Form
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- 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
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