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SHOX-Related Disorders, Sequencing
3001399
Ordering Recommendation

Order when a SHOX-related disorder is suspected and SHOX deletion/duplication analysis is negative.

Mnemonic
SHOX FGS
Methodology
Polymerase Chain Reaction/Sequencing
Performed
Sun-Sat
Reported
12-14 days
New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.
ARUP Consult®
Disease Topics
Specimen Required
Patient Preparation
 
Collect
Lavender (EDTA) or Pink (K2 EDTA). 
Specimen Preparation
Transport 3 mL whole blood. (Min: 1 mL) 
Storage/Transport Temperature
Refrigerated. 
Unacceptable Conditions
 
Remarks
 
Stability
Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months 
Reference Interval
Interpretive Data
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.

Note
Hotline History
View Hotline History
Components
Component Test Code*Component Chart NameLOINC
3001400SHOX FGS Specimen
3001406SHOX FGS Interpretation
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • Langer mesomelic dysplasia (LMD)
  • Leri-Weill dyschondrosteosis (LWD)
  • Short stature
  • SHOX