Cone-Rod Dystrophy via the PITPNM3 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
11589 PITPNM3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11589PITPNM381479 81479(x2) $890 Order Options and Pricing

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).

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

Cone-rod dystrophy (CORD/CRD) is a rare hereditary retinal disorder with a worldwide prevalence of ~1 in 40,000. CRD is characterized by dysfunction or degeneration of cone photoreceptors with relative preservation of rod function in the initial stages. The most common symptoms are photophobia and epiphora in bright light, decreased visual acuity, and dyschromatopsia. Fundus changes may vary from mild pigment granularity to a distinct atrophic lesion in the central macula. As the disease progresses, degeneration of rod photoreceptors also occurs and leads to progressive night blindness and peripheral visual field loss (Hamel 2007).

Genetics

Non syndromic CRD is genetically heterogeneous and exhibits autosomal dominant (ad), autosomal recessive (ar) and, rarely, X-linked (xl) inheritance (Hamel 2007). So far, about 25 genes have been implicated in different forms of CRD (RetNet). Mutations in PITPNM3 are associated with autosomal dominant CRD. PITPNM3 mutation analysis in two Swedish families (originating from the same geographical area in Northern Sweden) identified a mutation c.1878G>C (p.Q626H) in all affected family members (33/80), which showed consistent segregation with the disease. Shared haplotypes and presence of the c.1878G>C mutation in both families suggested that the families have a common ancestry (Köhn et al. 2007 and 2008). Only a few pathogenic variations in PITPNM3 have been reported, all missense, which are associated with autosomal dominant cone-rod dystrophy (Human Gene Mutation Database).

PITPNM3 (also called Nir3), which is located on 17p13 (Balciuniene et al. 1995) encodes phosphatidylinositol transfer (PIT) membrane-associated protein (PITPNM3). Three mammalian PIT membrane-associated proteins (PITPNM1, 2 and 3), are known as human homologues of the Drosophila retinal degeneration B (rdgB) protein that is involved in the phototransduction signaling pathway (Lev et al. 1999; Tian and Lev 2002). It is possible that PITPNM proteins also have a similar function.  PITPNM3 is shown to be highly expressed in the mammalian retina, specifically in the inner segment and in the inner and outer plexiform layers. PITPNMs are multidomain proteins that have six putative transmembrane domains, a calcium-binding region, and a carboxyterminal (C-terminal) domain. The C-terminal domain of PITPNMs functions as a PYK2 (a nonreceptor protein tyrosine kinase) -binding site and forms a PYK2 and PITPNM complex, which induces tyrosine phosphorylation of PITPNM proteins (Lev et al. 1999; Ocaka et al. 2005). Tyrosine phosphorylation in turn regulates calcium and phosphoinositide metabolism downstream of G-protein-coupled receptors (Lev et al. 1999).

Clinical Sensitivity - Sequencing with CNV PGxome

To study the global impact of PITPNM3 on retinal degenerations, Köhn et al. (2010) screened 163 patients from Denmark, Germany, UK, and the USA (Köhn et al. 2010). They detected PITPNM3 pathogenic variants in only 4 patients (~2%), which indicates that PITPNM3 is an uncommon cause of cone-rod dystrophies.

Testing Strategy

This test provides full coverage of all coding exons of the PITPNM3 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 Cone-rod dystrophy.

Gene

Official Gene Symbol OMIM ID
PITPNM3 608921
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Cone-Rod Dystrophy 5 AD 600977

Citations

  • Balciuniene J, Johansson K, Sandgren O, Wachtmeister L, Holmgren G, Forsman K. 1995. A gene for autosomal dominant progressive cone dystrophy (CORD5) maps to chromosome 17p12-p13. Genomics 30: 281–286. PubMed ID: 8586428
  • Hamel CP. 2007. Cone rod dystrophies. Orphanet J Rare Dis 1;2:7. PubMed ID: 17270046
  • Human Gene Mutation Database (Bio-base).
  • Köhn L, Kadzhaev K, Burstedt MSI, Haraldsson S, Hallberg B, Sandgren O, Golovleva I. 2007. Mutation in the PYK2-binding domain of PITPNM3 causes autosomal dominant cone dystrophy (CORD5) in two Swedish families. Eur. J. Hum. Genet. 15: 664–671. PubMed ID: 17377520
  • Köhn L, Kadzhaev K, Burstedt MSI, Haraldsson S, Sandgren O, Golovleva I. 2008. Mutation in the PYK2-binding domain of PITPNM3 causes autosomal dominant cone dystrophy (CORD5) in two Swedish families. Adv. Exp. Med. Biol. 613: 229–234. PubMed ID: 18188949
  • Köhn L, Kohl S, Bowne SJ, Sullivan LS, Kellner U, Daiger SP, Sandgren O, Golovleva I. 2010. PITPNM3 is an uncommon cause of cone and cone-rod dystrophies. Ophthalmic Genet. 31: 139–140. PubMed ID: 20590364
  • Lev S, Hernandez J, Martinez R, Chen A, Plowman G, Schlessinger J. 1999. Identification of a novel family of targets of PYK2 related to Drosophila retinal degeneration B (rdgB) protein. Mol. Cell. Biol. 19: 2278–2288. PubMed ID: 10022914
  • Ocaka L, Spalluto C, Wilson DI, Hunt DM, Halford S. 2005. Chromosomal localization, genomic organization and evolution of the genes encoding human phosphatidylinositol transfer protein membrane-associated (PITPNM) 1, 2 and 3. Cytogenet. Genome Res. 108: 293–302. PubMed ID: 15627748
  • Tian D, Lev S. 2002. Cellular and developmental distribution of human homologues of the Drosophilia rdgB protein in the rat retina. Invest. Ophthalmol. Vis. Sci. 43: 1946–1953. PubMed ID: 12037004

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

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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.
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