Zellweger Syndrome Subpanel


Zellweger syndrome spectrum is a group of peroxisomal disorders arising from a failure of protein import into the peroxisomal membrane or matrix. These peroxisome biogenesis disorders are genetically heterogeneous with at least 14 distinct genetic groups as identified from complementation studies. Peroxisome biogenesis disorders include Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes. While many of these patients present with severe disease in infancy, individuals diagnosed in childhood may first be identified through loss of hearing or vision.

The Zellweger Syndrome Subpanel includes nine genes. Our customizable targeted next-generation sequencing (NGS) panel uses Agilent SureSelect™ target enrichment and Illumina HiSeq sequencing. NGS technology is ideal for diagnostic testing of these disorders due to the extreme locus heterogeneity and phenotype overlap of the genes involved. The sensitivity of this panel is estimated at 99% for single-base substitutions.

If indicated, Sanger sequencing may be performed in both directions using BigDye Terminator chemistry with the ABI 3730 DNA analyzer with target specific amplicons. It may also be used to supplement specific guaranteed target regions that fail NGS sequencing or as a confirmatory method for NGS positive results. NGS technology may not detect all small insertions or deletions. Additionally, it is not diagnostic for large duplications or deletions, repeat expansions, and structural genomic variation. Therefore, multiplex ligation-dependent probe amplification (MLPA) and oligonucleotide array comparative genomic hybridization (aCGH) are available for this test for deletion/duplication analysis. MLPA copy number analysis is available for the DFNB1 (GJB2/GJB6) locus, OTOA, and STRC. This MLPA testing is approximately 99% accurate. The customized oligonucleotide microarray is a highly-targeted, exon-focused array capable of detecting microdeletions and microduplications at a much higher resolution than traditional aCGH methods. The sensitivity of the aCGH assay is estimated to be greater than 99% for medically-relevant microdeletions and microduplications in the exonic regions of nine genes.


Specimen Requirements

Prenatal

Please provide one of the following specimen types:

  • Two confluent T-25 flasks of cultured cells from amniotic fluid or chorionic villi
  • >4 mg of direct chorionic villi tissue
  • 15 mL of direct amniotic fluid

5-10 mL of blood in an EDTA tube (lavender top) is required from each biological parent. Parental blood samples may be used for maternal cell contamination studies or confirmation studies.

Whole blood

Newborn or child
  • One 2 mL EDTA tube (lavender top) or one 2 mL ACD-A or ACD-B tube (yellow top) from the patient
  • One 5-10 mL EDTA tube (lavender top) or one 5-10 mL ACD-A or ACD-B tube (yellow top) is also recommended from each biological parent

Adult
  • Two 5-10 mL EDTA tubes (lavender top) or two 5-10 mL ACD-A or ACD-B tubes (yellow top) from the patient
  • One 5-10 mL EDTA tube (lavender top) or one 5-10 mL ACD-A or ACD-B tube (yellow top) is also recommended from each biological parent

Extracted DNA

  • A minimum of 10 μL DNA (50-250 ng/μL) is required for testing. 20 μL DNA (50-350 ng/μL) is recommended

Saliva

  • Saliva specimens are accepted upon request. Please contact our laboratory to obtain saliva kits
  • Saliva samples should be collected in Oragene DNA (OG-500) kits by DNA Genotek

Ordering Information

Shipping

  • Tubes of blood, cultured cells, direct chorionic villus sampling, and direct amniotic fluid should be stored and shipped at room temperature or refrigerated
  • Do not freeze specimens
  • Please ship specimens same day or overnight to: 1428 Madison Ave, Atran Bldg, Rm 2-25, New York, NY 10029

Turnaround Time

  • Prenatal: 7-10 business days from receipt of specimen
  • Pediatric or adult: 3-4 weeks from receipt of specimen


Resources

Hearing and Vision Loss Test Requisition
Genetic Testing for Hearing and Vision Loss Brochure