Test Directory

Test Code
2106
Test Name
Pseudoxanthoma Elasticum NGS Panel
CPT Codes
81479
Expected Turnaround Time
Typically 2 to 4 weeks from receipt of a sample in the laboratory. All cases involving ongoing pregnancies will be expedited.
Clinical Utility
Genetic analysis to provide a molecular diagnosis of this disorder. Recommended for individuals with a personal and/or family history of this disorder to ensure appropriate treatment and establish recurrence risk for family members.
Specimen and Container Info

Non-Prenatal Specimens

Preferred/Alternate

Specimen Type

Containers

Volume

Preferred Specimen Type

Whole Blood

Lavender Top (EDTA)

3 mL

Alternate Specimen Type

Genomic DNA

1.5 mL Tube

3 µg (at a concentration of at least 30 ng/µl), preferably in TE solution.

Alternate Specimen Type

Fibroblasts

T-25 Flasks

2 confluent T-25 flasks, filled to capacity

Alternate Specimen Type

Saliva (Whole blood is recommended for CNV)

DNA Self-Collection Kit or Oragene Saliva Collection Kit for Young Children

Follow kit instructions (www.dnagenotek.com)

Prenatal Specimens

Either specimen type below is acceptable.

Specimen Type

Containers

Volume

Cultured cells

T-25 Flasks

2 confluent T-25 flasks derived from amnio or CVS samples.

Genomic DNA

1.5 mL Tube

3 µg (at a concentration of at least 30 ng/µl), preferably in TE solution.

NOTE: For specimens from outside of North America, the preferred specimen type is Genomic DNA. HNL Genomics does not recommend shipping whole blood or cultured cells from any location other than the United States, Canada, or Mexico.

Transport Instructions
  • Transport at room temperature within 24 hours.
  • If the specimen cannot be transported to the lab within 24 hours, refrigerate for up to 72 hours.
  • Do not freeze or expose to extreme temperatures, refrigerate for up to 72 hours if cannot be transported to lab within 24 hours. 
Stability Requirements

Room Temperature

24 hours

Refrigerated

72 hours

Causes for Rejection
  • Improperly labeled specimen (minimum of two patient identifiers)
  • Inappropriate specimen type
  • Incomplete or incorrect test request form
  • Insufficient volume
  • Specimen has leaked in transit
  • Specimen without a test order
Methodology
Next Generation Sequencing and Copy Number Variation Analysis
Performing Location
Genomics - Snowdrift
Alternate Names
PXE
Description

Pseudoxanthoma elasticum (PXE; MIM 264800) is an autosomal recessive disorder, characterized by ectopic mineralization and fragmentation of the elastic fibers. The clinical findings are progressive and primarily involve the skin, eyes and cardiovascular system. The skin of the neck and flexural areas displays yellow papules or plaques and eventually becomes lax, redundant and inelastic. Retinal angioid streaks representing disruption of Bruchs%u2019 membrane are present in the majority of patients. Pigmentary changes, macular degeneration, retinal hemorrhage, choroidal neovascularization and other changes contribute to vision impairment in more than 50% of patients. Endocardial calcifications, coronary artery disease, severe atherosclerosis, arteriosclerosis, reduced or absent pulses with intermittent claudication, congestive heart failure and renovascular hypertension represent cardiovascular manifestation. PXE is considered a metabolic disease caused by mutations in the ATP-binding cassette, subfamily C, membrane 6 gene (ABCC6). This molecule is a transmembrane transporter, primarily expressed in the liver, whose exact role in arterial and tissue calcification remains elusive. Mutations in ABCC6 have also been described in generalized arterial calcification of infancy 2 (GACI2; MIM 614473), a usually fatal disorder with early onset. Additionally, several patients with mutations in the ENPP1 gene have been reported to have clinical features of generalized arterial calcification of infancy 1 (GACI1; MIM 208000) and PXE. The incidence of PXE has been estimated at 1:25,000-1:50,000.

Pseudoxanthoma elasticum-like disorder with multiple coagulation factor deficiency (MIM 610842) shares many of the clinical features of PXE, but patients also have excessive skin folding, resembling cutis laxa, and deficiency of vitamin K-dependent coagulation factors. The primary differences from PXE include no decrease in visual acuity and more widespread skin laxity involving the trunk and limbs, in addition to flexural areas. This disorder is caused by autosomal recessive mutations in the gamma-glutamyl carboxylase gene (GGCX). Additionally, digenic mutations in ABCC6 and GGCX have been reported in siblings with skin findings of PXE but no coagulation disorder.

Testing Schedule
Monday-Friday
Genes
ABCC6, GGCX
MIM
264800, 610842
Disease Group
Hair and Nail disorders, Skin, Tooth