Retinal Disease Subpanel


Retinitis pigmentosa (RP) is a group of inherited disorders in which abnormalities of the photoreceptors (rods and cones) or the retinal pigment epithelium of the retina lead to progressive visual loss. Affected individuals first experience defective dark adaptation or “night blindness,” followed by constriction of peripheral visual fields. Many patients with RP retain a small degree of central vision throughout their life, but eventually loss of central vision may occur late in the course of the disease. RP can be isolated (non-syndromic) or syndromic (part of a disease affecting multiple tissues and organs).

Main syndromic causes of RP are the ciliopathies, diseases caused by dysfunctional cilia. These diseases include Leber congenital amaurosis (LCA), Bardet-Biedl syndrome (BBS), Joubert syndrome (JS), and Senior-Loken syndrome (SLS). Leber congenital amaurosis manifests with vision loss at birth or in early infancy. Patients have profound loss of vision at an early age, and some have been reported to have intellectual disability. Bardet-Biedl syndrome is characterized by obesity, intellectual disability, kidney disease, and loss of vision, beginning with loss of night vision and progressing to tunnel vision and blindness. Clinical features of Joubert syndrome include intellectual disability, brain malformations, ocular problems (including uncontrollable eye movements and loss of vision), and kidney cysts leading to end-stage renal disease. Senior-Loken syndrome is characterized by LCA and renal cysts and dysfunction, leading to end-stage renal disease.

The Retinal Disease Subpanel includes 154 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, oligonucleotide array comparative genomic hybridization (aCGH) is available for this test for deletion/duplication analysis. 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 153 genes. Copy number variation of RAB28 will not be reported using aCGH.


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