Hereditary Coproporphyria: CPOX Sequencing

Diagnostic Use

Hereditary Coproporphyria (HCP) is a low penetrance, autosomal dominant disorder which presents with excessive accumulation and excretion of protoporphyrin. Symptoms include skin lesions and/or acute neurovisceral attacks. Approximately 75% of affected individuals remain asymptomatic, but are at risk if exposed to certain drugs, alcohol or other factors. HCP is caused by a partial deficiency of coproporphyrinogen oxidase (CPOX), which catalyses the penultimate reaction in heme biosynthesis. The enzyme is located in the inner membrane of mitochondria in various tissues, primarily the liver. The CPOX gene spans 18 kb on chromosome 3 and contains 7 exons.

Department

Genetics - Molecular Pathology

Delphic Registration Code

MOLP

Synonyms

HCP

Turnaround Time

4 weeks

Specimen Type

• Whole Blood

Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

4.0

No of Samples Required

1

Paediatric Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

1.0

Minimum Sample Volume (ml)

0.5

Additional Specimen Information

If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Aliquot Instructions

Sample Type

• Whole Blood

Transport to Lab

Ambient (8 - 24 degrees Celsius)

Additional Referral/Aliquot Information

If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Test Method

Screening of the CPOX gene involves sequencing of all coding exons (1–7) and their flanking regions. This method should detect all small mutations in the coding region of CPOX, as well as defects in the intronic areas immediately bordering the exon that may affect splicing. Large inversions, insertions and deletions will not be detected, nor will promoter region mutations.

Contact Canterbury Health Laboratories on +64 3 364 0484 or email LabInfo@cdhb.health.nz

Uncertainty of Measurement:
Automated bidirectional DNA sequencing has an analytical sensitivity and specificity of >99%. Note that the lower limit of variant detection of sequencing analysis is ~10%, this is important to consider in the case of mosaicism, mitochondrial, and somatic variation that is not expected to be present at 50% or 100%. This analysis will not detect variants located within intronic regions, except at the intron-exon boundaries.

Contact Information

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