Late-Onset Autosomal Dominant Retinitis Pigmentosa 42 (RP42) and Crisponi/Cold-Induced Sweating Syndrome Type 1(CISS1)-Like Phenotype Associated with Early-Onset Autosomal Recessive Retinitis Pigmentosa via the KLHL7 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
10499 KLHL7 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
10499KLHL781479 81479 $890 Order Options and Pricing

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

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Clinical Features and Genetics

Clinical Features

Retinitis pigmentosa (RP) represents a group of hereditary retinal dystrophies with a worldwide prevalence of ~1 in 4,000 (Booij et al. 2005. PubMed ID: 16272259). 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. PubMed ID: 10025514).

Crisponi syndrome (CS)/cold-induced sweating syndrome type 1 (CISS1)-like phenotype is a complex phenotype and genetically heterogeneous disorder, which is inherited in an autosomal recessive manner. CS/CISS1-like Phenotype is characterized by hyperthermia and feeding difficulties in the neonatal period, scoliosis, and paradoxical sweating induced by cold in early childhood with high neonatal lethality.

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 AD, AR, and XL RP, respectively (RetNet).

Pathogenic variants in KLHL7 have been documented causative for late-onset ADRP or Crisponi/CISS1-like phenotype associated with early-onset ARRP (Friedman et al. 2009. PubMed ID: 19520207; Angius et al. 2016. PubMed ID: 27392078). KLHL7 encodes a BTB-Kelch related protein, which is highly expressed in rod photoreceptor cells. This protein participates as an adaptor and/or chaperone in the ubiquitination of target proteins through Cullin E3 ligases for proteasome-mediated degradation. This protein consists of one BTB (codons 44 through 111), one BACK (codons 146 through 248) and one Kelch domain (also known as Kelch repeat β-propeller domain; codons 294 through 575) (Friedman et al. 2009. PubMed ID: 19520207). The variants that cause ADRP have been reported to be clustered in the BACK domain, and the variants that cause CS/CISS1-like Phenotype associated ARRP affect the kelch domain. Bi-allelic variants in this gene may lead to complete failure in the ubiquitination of the target substrate(s) and may result in severe CS/CISS1-like Phenotype (Angius et al. 2016. PubMed ID: 27392078). To date, ~10 pathogenic variants (missense and a small frameshift deletion and splicing) in KLHL7 have been connected to RP (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

Friedman et al. estimated that the KLHL7 accounts for 1-2% of the autosomal dominant retinitis pigmentosa cases (Friedman et al. 2009. PubMed ID: 19520207). However, predicting clinical sensitivity for this gene for the Crisponi/CISS1-like phenotype associated with early-onset autosomal recessive retinitis pigmentosa is challenging due to the limited number of cases.

Testing Strategy

This test provides full coverage of all coding exons of the KLHL7 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

All patients with symptoms suggestive of RP and CS/CISS1-like Phenotype are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in KLHL7.

Gene

Official Gene Symbol OMIM ID
KLHL7 611119
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Cold-Induced Sweating Syndrome 3 AR 617055
Retinitis Pigmentosa 42 AD 612943

Related Tests

Name
Autosomal Recessive Retinitis Pigmentosa 77 (RP77) via the REEP6 Gene
Retinitis Pigmentosa (includes RPGR ORF15) Panel

Citations

  • Angius et al. 2016. PubMed ID: 27392078
  • Booij et al. 2005. PubMed ID: 16272259
  • Friedman et al. 2009. PubMed ID: 19520207
  • Human Gene Mutation Database (Bio-base).
  • RetNet: Genes and Mapped Loci Causing Retinal Diseases.
  • van Soest et al. 1999. 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.

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

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ORDER OPTIONS

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