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Refsum Disease NGS Panel

Genes:
PEX7;
PHYH

Syndrome Information

Clinical Description

Patients with Refsum disease have significantly elevated plasma phytanic acid.  The most constant clinical features include retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, anosmia, and deafness.  The majority of patients have a defect in the enzyme phytanoyl-CoA 2-hydroxylase that is encoded by PHYH.  A subset of patients (<10%) have mutations in PEX7.  Although most patients with PEX7 defects have biochemical and clinical features consistent with rhizomelic chondrodysplasia punctate type 1, a small portion have a milder defect that overlaps clinically and biochemically with Refsum disease.

Inheritance Pattern

Autosomal Recessive

Genotype-Phenotype Correlation

Missense mutations may be associated with milder clinical and biochemical phenotypes.

Test Information

Test Method

Next Generation Sequencing (NGS) of the coding regions and intron-exon boundaries of the listed genes;Deletion/Duplication:  Dosage analysis by normalization of NGS read depth for the listed genes; Sanger sequencing for potential fill in / confirmation 

This test is also available as part of one or more NGS panels for peroxisomal disorders.

Clinical Utility

Identification of causative mutations in known or highly suspicious cases of Refsum Disease based on clinical presentation and the blood biomarker profile; discrimination between Refsum disease and mild rhizomelic chondroplasia punctata (RCDP) Type 1; targeted carrier testing of relatives of proband; predictive prenatal testing when familial mutations are known. 

Clinical Sensitivity

This testing detects PHYH and PEX7 defects in > 90% and <10% of Refsum disease patients, respectively.  This analysis will identify two mutations in the same gene in >98% of patients.  There have been individual case reports of deletions/duplications in the PEX7 or PHYH genes, but no published case series.  

Analytic Sensitivity

Missense mutations may be associated with milder clinical and biochemical phenotypes.
>99% for inherited single nucleotide and small insertion/deletion variants for the nucleotides evaluated; >99% for multi-exon deletions and >98% for single exon deletions; >90% for multi-exon duplications and >75% for single exon duplications. Lower limit of detection for single nucleotide variants: 25% allele frequency (>99% sensitivity).

Sample Requirements

3-6ml whole blood in EDTA (purple topped) tubes. (see Pediatric or Adult blood sample algorithms for additional information)

We prefer whole blood for all tests.

Turn Around Time

Approximately 4 weeks

Fee and CPT Codes

$2450 for routine testing
CPT Code: 81479 x 2

Special Considerations

We request that copies of the patient's biochemical analysis be submitted with the sample.

This test is also available as part of one or more NGS panels for peroxisomal disorders

INFORMED CONSENT from the patient is required prior to ordering a genetic test. The DNA Diagnostic Lab's consent is located on the second page of the requisition form. There is also a patient brochure, "Things Every Patient Should Know Before Consenting to a Genetic Test", available for download.