Order when a SHOX-related disorder is suspected and SHOX deletion/duplication analysis is negative.
Polymerase Chain Reaction/Sequencing
Lavender (EDTA) or Pink (K2 EDTA).
Transport 3 mL whole blood. (Min: 1 mL)
Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months
Background Information for SHOX-Related Disorders, Sequencing:
Characteristics of SHOX-related disorders (SHOX deficiency): Short stature, mesomelia, and abnormal alignment of the radius, ulna and carpal bones at wrist (Madelung deformity). Variable expressivity results in some affected individuals with syndromic short stature and additional findings (eg, Leri-Weill dyschondrosteosis (LWD) or Langer mesomelic dysplasia (LMD)), while others have isolated short stature (ISS).
Prevalence of SHOX deficiency: 1 in 1,000
Inheritance: SHOX is located in pseudoautosomal region 1 (PAR1) on the X and Y chromosomes and escapes X-inactivation. Thus, inheritance is pseudoautosomal dominant for ISS and LWD, and pseudoautosomal recessive for LMD.
Penetrance: High, with variability in expression.
Cause: One pathogenic variant (haploinsufficiency) of the SHOX gene causes ISS and LWD. Two pathogenic variants in SHOX (complete loss of SHOX) cause LMD.
Clinical Sensitivity: Approximately 10-20 percent of disease-causing variants in SHOX are sequence variants.
Methodology: Bidirectional Sanger sequencing of the SHOX coding regions, including exon 6a and 6b, and intron-exon boundaries.
Analytical Sensitivity and Specificity: Greater than 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Large deletions/duplications, repeat element insertions, deep intronic variants, and some regulatory region variants are not detected.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.
Compliance Statement C: For human genetic inheritable conditions and mutations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|3001400||SHOX FGS Specimen|
|3001406||SHOX FGS Interpretation|
- Langer mesomelic dysplasia (LMD)
- Leri-Weill dyschondrosteosis (LWD)
- Short stature