Molecular Genetics Huntington Disease

Huntington Disease (HD) is an inexorably progressive, generally adult onset disorder, characterized by mood and personality changes, clumsiness, chorea, and cognitive decline.  HD is an autosomal dominant disorder caused by the expansion in size of a polymorphic CAG trinucleotide repeat located at the 5'-end of the HTT (also known as HD or IT15) gene.  This gene has been mapped to chromosome 4p16.3.
 
The mean age of adult onset HD is 35 to 44 years with death occurring approximately 15 to 18 years after the onset of symptoms.  Individuals with 36 to 40 CAG repeats may or may not develop Huntington disease, while people with more than 40 repeats almost always develop the disorder.  Individuals with juvenile onset have HD symptoms prior to the age of 20 years and have CAG repeats greater than 60.

Reason for Referral:
The Huntington Disease assay is clinically indicated for the evaluation of:

• Symptomatic patients with a suspected diagnosis of HD.
• Presymptomatic patients with a family history of HD and therefore at risk to have inherited a mutant HD allele.

 

Mutation analysis by Triplet Repeat PCR to identify the number of CAG trinucleotide repeats responsible for Huntington disease.

Interpretation:

# of CTG Repeats	Interpretation
10-26	No clinical phenotype
27-35	Indeterminate
36-39	Mutant Allele.  Indeterminate clinical phenotype.  Symptoms may not appear in patient's lifetime.
≥40	Clinically affected or likely to become symptomatic in the future.

Blood: EDTA or ACD (Solution A or B):

Adult: 5 mL

Child: 5 mL

Infant: 2-3 mL

Saliva: 2 ORAgene™ Saliva Collection Kits (OGR-500) used according to manufacturer instructions.  Please contact KDL Client Services for a Saliva Collection Kit for patients that cannot provide a blood sample.

Assisted Saliva: 4 ORAgene™ Assisted Saliva Collection Kits (OGR-575) used according to manufacturer instructions.  Please contact KDL Client Services for an Assisted Saliva Collection Kit for patients that cannot provide a blood sample.

DNA: 200 ng at a minimum of 50-100 ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

Prenatal:

Direct Amniotic Fluid (10-20mL)

Direct CVS

Cultured Amniocytes (2 T-25 flasks)

Cultured CVS (2 T-25 flasks)

Cultured Fetal Tissue: Product of Conception (2 T-25 flasks)

Cord Blood (1-2mL)

Notice Regarding Molecular Genetic Testing on CVS or Amniotic Fluid Specimens:

Maternal cell rule-out testing will be performed on all prenatal specimens received. Please provide maternal blood in addition to the fetal specimen. Additional charges apply for the maternal cell rule-out test.

All genetic testing performed on Direct CVS or Amniotic Fluid specimens will be confirmed on cell cultures prepared by Knight Diagnostic Laboratories. Cell cultures will be prepared from the specimen received. Additional charges apply for confirmatory testing.

For routine testing of blood and saliva (or DNA extracted from them), KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion.  For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

An ordering physician statement must also accompany all requests.  Please contact Client Services at (855) 535-1522 for appropriate requisition and forms.

Weekly

14-21 Days

• Package and ship specimen to remain cold, but not frozen. 
• Ship via overnight express, using the FedEx priority overnight label provided. 
• Contact Client Services for shipping kits and instructions at (855) 535-1522.

1. Mohamed Jama, Alison Millson, Christine E. Miller, and Elaine Lyon.  Triplet Repeat Primed PCR Simplifies Testing for Huntington Disease.  The Journal of Molecular Diagnostics, vol. 15, No. 2, March 2013.

Testing is diagnostic for normal/presymptomatic/disease states. Extensive experience with affected individuals and their families has indicated that it is mandatory for individuals requesting presymptomatic testing to participate in an approved multidisciplinary Huntington disease testing protocol.  Please contact Client Services at (855) 535-1522 prior to drawing samples.