DNA icon

Autosomal Dominant Retinitis Pigmentosa 48 (RP48) via the GUCA1B Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
9069 GUCA1B 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9069GUCA1B81479 81479,81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Dana Talsness, PhD

Clinical Features and Genetics

Clinical Features

Retinitis pigmentosa (RP; OMIM # 268000) or rod cone dystrophies (RCDs) represent a group of hereditary retinal dystrophies with a worldwide prevalence of ~1 in 4000 (Booij et al., 2005). RP is clinically characterized by retinal pigment deposits visible on fundus examination, nyctalopia ("night blindness"), followed by progressive degeneration of the photoreceptors, which eventually leads to blindness (van Soest et al., 1999). RP48 is typically characterized as RP with or without macular involvement (Sato et al., 2005).

Genetics

Nonsyndromic RP is remarkably heterogeneous both clinically and genetically and exhibits autosomal dominant (ad), autosomal recessive (ar) or X-linked (XL) inheritance. To date, over 50 loci have been linked to nonsyndromic RP and 18, 27 and 2 genes have been identified that are associated with adRP, arRP, and XLRP, respectively (RetNet). Visual photransduction is a biochemical process responsible for light conversion into electrical signals in the rod and cone cells. Photoreceptor guanylate cyclase 1 (GC1/retGC-1), encoded by GUCY2D, helps in restoring photoreceptor sensitivity by synthesizing cyclic guanosine monophosphate (cGMP), which is regulated by guanylate cyclase activator proteins (GCAPs: 1 and 2). These proteins are mainly expressed in the outer segments of the photoreceptors (Jiang and Baehr, 2010). GCAPs 1 and 2 are encoded by GUCA1A and GUCA1B, respectively. GCAPs are sensitive to changes in cytoplasmic Ca2+ concentrations. It has been reported that GCAP2 is activated at lower Ca2+ concentrations than GCAP1 (Hwang et al., 2003). However, GCAP1 and GCAP2 regulate the Ca2+ signaling of GC1 in different ways. Even in the absence of GCAP2, GCAP1alone can restore the recovery of rod and cone responses, whereas GCAP2 can only partially compensate (Kitiratschky et al., 2009) Thus GCAP1 plays major role in regaining the dark-adapted state after excitation of the photoreceptor (Mendez et al., 2001; Pennesi et al., 2003). Disruption of Ca2+ homeostasis, due either to genetic or environmental factors leads to apoptosis of the photoreceptor cells (Baehr and Palczewski., 2007; Garcia-Hoyos et al., 2011). So far, about five causative missense mutations in GUCA1B have been associated with ad retinal degeneration (Nishiguchi et al., 2004).

Clinical Sensitivity - Sequencing with CNV PGxome

GUCA1B mutation analysis in 63 unrelated patients with adRP and 33 patients with arRP, identified a heterozygous GUCA1B mutation in three index patients from three independent families (~3%)(Sato et al., 2005). This study observed that the mutation caused variable phenotypic expression with incomplete penetrance. In another study, the GUCA1B gene was analyzed in 421 patients with retinal degeneration and five rare variants in a total of six heterozygous patients (~1%) were identified (Nishiguchi et al., 2004).

So far, no gross deletions or duplications have been reported in GUCA1B (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the GUCA1B gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

All patients with symptoms suggestive of adRP with or without macular involvement.

Gene

Official Gene Symbol OMIM ID
GUCA1B 602275
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Retinitis Pigmentosa 48 613827

Related Test

Name
Retinitis Pigmentosa (includes RPGR ORF15) Panel

Citations

  • Baehr W and Palczewski K. 2007. Guanylate cyclase-activating proteins and retina disease. Subcell Biochem 45:71-91. PubMed ID: 18193635
  • Booij JC. et al. 2005. Journal of medical genetics. 42: e67. PubMed ID: 16272259
  • Garcia-Hoyos M, Auz-Alexandre CL, Almoguera B, Cantalapiedra D, Riveiro-Alvarez R, Lopez-Martinez MA, Gimenez A, Blanco-Kelly F, Avila-Fernandez A, Trujillo-Tiebas MJ, Garcia-Sandoval B, Ramos C, Ayuso C. 2011. Mutation analysis at codon 838 of the Guanylate Cyclase 2D gene in Spanish families with autosomal dominant cone, cone-rod, and macular dystrophies. Mol. Vis. 17:1103-1109. PubMed ID: 21552474
  • Human Gene Mutation Database (Bio-base).
  • Hwang JY, Lange C, Helten A, Höppner-Heitmann D, Duda T, Sharma RK, Koch KW. 2003. Regulatory modes of rod outer segment membrane guanylate cyclase differ in catalytic efficiency and Ca(2+)-sensitivity. Eur. J. Biochem. 270: 3814–3821. PubMed ID: 12950265
  • Jiang L, Baehr W. 2010. GCAP1 Mutations Associated with Autosomal Dominant Cone Dystrophy. In: Anderson RE, Hollyfield JG, and LaVail MM, editors. Retinal Degenerative Diseases, New York, NY: Springer New York, p 273–282. PubMed ID: 20238026
  • Kitiratschky VB, Behnen P, Kellner U, Heckenlively JR, Zrenner E, Jägle H, Kohl S, Wissinger B, Koch K-W. 2009. Mutations in the GUCA1A gene involved in hereditary cone dystrophies impair calcium-mediated regulation of guanylate cyclase. Human mutation 30: E782–E796. PubMed ID: 19459154
  • Mendez A, Burns ME, Sokal I, Dizhoor AM, Baehr W, Palczewski K, Baylor DA, Chen J. 2001. Role of guanylate cyclase-activating proteins (GCAPs) in setting the flash sensitivity of rod photoreceptors. Proceedings of the National Academy of Sciences 98:9948-9953. PubMed ID: 11493703
  • Nishiguchi KM. 2004. A Novel Mutation (I143NT) in Guanylate Cyclase-Activating Protein 1 (GCAP1) Associated with Autosomal Dominant Cone Degeneration. Investigative Ophthalmology & Visual Science 45: 3863–3870. PubMed ID: 15505030
  • Pennesi ME, Howes KA, Baehr W, Wu SM. 2003. Guanylate cyclase-activating protein (GCAP) 1 rescues cone recovery kinetics in GCAP1/GCAP2 knockout mice. Proceedings of the National Academy of Sciences 100: 6783–6788. PubMed ID: 12732716
  • RetNet
  • Sato M, Nakazawa M, Usui T, Tanimoto N, Abe H, Ohguro H. 2005. Mutations in the gene coding for guanylate cyclase-activating protein 2 (GUCA1B gene) in patients with autosomal dominant retinal dystrophies. Graefes Arch. Clin. Exp. Ophthalmol. 243: 235–242. PubMed ID: 15452722
  • van Soest S, Westerveld A, Jong PT de, Bleeker-Wagemakers EM, Bergen AA. 1999. Retinitis pigmentosa: defined from a molecular point of view. Surv Ophthalmol 43: 321–334. PubMed ID: 10025514

Ordering/Specimens

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


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
×
Copy Text to Clipboard
×