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Rhizomelic Chondrodysplasia Punctata Type 1 and Adult Refsum Disease via the PEX7 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
PEX7 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7273PEX781479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Greg Fischer, PhD

Clinical Features and Genetics

Clinical Features

Mutations in PEX7 can lead to Rhizomelic Chondrodysplasia Punctata (RCDP) type 1 or relatively mild adult Refsum disease (ARD). Rhizomelic Chondrodysplasia Punctata (RCDP) is neonatal onset and characterized by proximal shortening of the long bones (rhizomelia), multiple epiphyseal calcifications and joint contractures, cataracts, dysmorphic facies, profound intellectual disability and growth deficiency. RCDP type 1 is the most common and classic type of RCDP and is clinically indistinguishable from type 2 or 3. Most patients with RCDP type 1 die in the first or second year, few survive beyond the first decade of life (Braverman et al. 2012; Purdue et al. 1997).

Adult Refsum disease (ARD) usually develops in late childhood with the first set of clinical symptoms including anosmia, night blindness, and progressive retinitis pigmentosa. In the following 10-15 years, other symptoms including peripheral neuropathy, nerve deafness, cerebellar ataxia, ichthyosis, skeletal dysplasia, and cardiac arrhythmias may occur. Unexplained remission has been observed in some patients. Most ARD cases are due to deficiency of phytanoyl-CoA hydroxylase, encoded by the PHYH gene. PEX7 defects account for less than 10% of all reported patients (Wanders et al. 2010; Braverman et al. 2002; van den Brink et al. 2003).


RCDP type 1 is inherited in an autosomal recessive manner and caused by PEX7 defects. Reported mutation spectrum includes missense, nonsense, splicing site mutations, and small deletion/insertions. Among studied patients with European ancestry, p.Leu292X was the most common (~50 %) due to a founder effect, followed by three other mutations (c.903+1G>C, p.Gly217Arg, and p.Ala218Val), together accounting for 15-20% of pathogenic alleles (Braverman et al. 2002; Motley et al. 2003).

PEX7-associated ARD is recessively inherited and expected to be very rare since less than 10 patients have been reported to date. Although not completely proven, it is presumed that residual function of the mutant PEX7 protein is correlated with milder phenotype in patients with ARD or RCDP Type 1 (Braverman et al. 2002; van den Brink et al. 2003). RCDP type 2 and type 3 are due to defects in GNPAT or AGPS, respectively, which encode enzymes required for plasmalogen synthesis in peroxisomes.

The PEX7 gene encodes the cytosolic receptor protein that specifically imports the PTS2-containing enzymes into peroxisomes. There are only three peroxisomal PTS2 enzymes (thiolase, PHYH, and AGPS), which play critical roles in α-oxidation of branched-chain lipids (e.g. phytanic acid) and plasmalogen synthesis. Peroxisomal enzymes involved in VLCFAs metabolism are imported by the PTS1 receptor (PEX5). Therefore, metabolic characteristics found in both RCDP type 1 and ARD patients include elevated plasma phytanic acid and deficient plasmalogen synthesis but normal levels of VLCFAs (C24:0 and C26:0) (Braverman et al. 2012; van den Brink et al. 2003)

Clinical Sensitivity - Sequencing with CNV PG-Select

In two unrelated cohorts, PEX7 mutations were found in > 90% of patients clinically diagnosed with RCDP. The founder mutation p.Leu292X has a high frequency in individuals of Northern European descent (Braverman et al. 2002; Motley et al. 2003).

No gross deletions/duplications have been reported so far in PEX7.

Testing Strategy

This test provides full coverage of all coding exons of the PEX7 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Individuals with clinical symptoms and biochemical findings consistent with RCDP Type 1 or patients clinically diagnosed with ARD, but not carrying PHYH mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PEX7.


Official Gene Symbol OMIM ID
PEX7 601757
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


  • Braverman et al. 2012. PubMed ID: 20301447
  • Braverman N, Chen L, Lin P, Obie C, Steel G, Douglas P, Chakraborty PK, Clarke JTR, Boneh A, Moser A, Moser H, Valle D. 2002. Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype. Hum. Mutat. 20: 284297. PubMed ID: 12325024
  • Motley AM, Brites P, Gerez L, Hogenhout E, Haasjes J, Benne R, Tabak HF, Wanders RJA, Waterham HR. 2002. Mutational spectrum in the PEX7 gene and functional analysis of mutant alleles in 78 patients with rhizomelic chondrodysplasia punctata type 1. Am. J. Hum. Genet. PubMed ID: 11781871
  • Purdue PE, Zhang JW, Skoneczny M, Lazarow PB. 1997. Rhizomelic chondrodysplasia punctata is caused by deficiency of human PEX7, a homologue of the yeast PTS2 receptor. Nat. Genet. 15: 381384. PubMed ID: 9090383
  • van den Brink DM, Brites P, Haasjes J, Wierzbicki AS, Mitchell J, Lambert-Hamill M, Belleroche J de, Jansen GA, Waterham HR, Wanders RJA. 2003. Identification of PEX7 as the second gene involved in Refsum disease. Am. J. Hum. Genet. 72: 471477. PubMed ID: 12522768
  • Wanders RJ, Waterham HR, Leroy BP. 2010. Refsum Disease. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301527


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

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