McLeod Syndrome via the XK 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
8767 XK 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8767XK81479 81479(x2) $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

  • Luke Drury, PhD

Clinical Features and Genetics

Clinical Features

McLeod Syndrome (MLS) is a progressive multi-system disorder with hematologic, neuromuscular, and central nervous system involvement. MLS is a subtype of neuroacanthocytosis syndrome which is characterized by degeneration of the basal ganglia leading to motor, cognitive, and psychiatric impairment. Acanthocytosis, spike protrusions in erythrocytes, is typically the first indication of MLS and present in asymptomatic individuals. Onset of neurological symptoms such as chorea, involuntary movements, and vocalizations ranges from 25-60 years old with disease duration potentially extending beyond 30 years. Psychiatric manifestations include depression, schizophrenia-like psychosis and obsessive compulsive disorder which typically presents prior to motor and cognitive dysfunction. About 60% of patients develop cardiomyopathy which is the leading cause of death in individuals with MLS (Danek et al. 2001; Jung et al. 2011; Jung et al. 2004). Genetic testing is helpful in the differential diagnosis of MLS from Huntington’s disease and other neuroacanthocytosis syndromes including Chorea-acanthocytosis, Huntington’s disease-like 2 and pantothenate kinase associated neurodegeneration (Jung et al. 2011).

Genetics

MLS is inherited in an X-linked recessive manner with complete penetrance through mutations in the XK gene. Males are predominantly affected, however, there have been rare instances of heterozygous females presenting with MLS (Ho et al. 1996). Most pathogenic mutations to date are null mutations including nonsense, splice site alterations, small insertions/deletions, and gross deletions which have been reported throughout the XK gene (Danek et al. 2001; Ho et al. 1994; Jung et al. 2004). MLS has also been reported to be part of a contiguous gene syndrome including chronic granulomatous disease (CYBB), Duchenne muscular dystrophy (DMD), and retinitis pigmentosa (RPGR) (Peng et al. 2007). Mutations in the XK gene lead to loss of or truncation of the XK protein Kell binding domain. This interaction is important for surface expression of Kell antigens which are important determinants of blood type (Ho et al. 1994). The exact function of XK is unknown but studies of an analogous C. elegans gene, ced-8, suggest it may be involved in regulating apoptosis (Stanfield et al. 2000).

Clinical Sensitivity - Sequencing with CNV PGxome

Mutations in the XK gene are the only reported cause of MLS. In a study of 22 MLS patients, XK mutations were found in each case with one patient exhibiting a deletion of the entire gene (Danek et al. 2001). Analytical sensitivity is >85% for detection of causative mutations in the XK gene. Gross deletions have been reported in a minority of cases (Peng et al. 2007; Danek et al. 2001).

Testing Strategy

This test provides full coverage of all coding exons of the XK 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

Patients with clinical features consistent with McLeod Syndrome including choreiform movements, peripheral neuropathy with areflexia, and cognitive impairment are candidates for testing. Common laboratory findings include weak to no Kell antisera reaction, acanthocytes, elevated serum creatine kinase (300-3000U/L), and MR imaging displaying progressive atrophy of the caudate nucleus (Danek et al. 2001; Jung et al. 2011; Jung et al. 2004).

Gene

Official Gene Symbol OMIM ID
XK 314850
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
McLeod Syndrome XL 300842

Citations

  • Danek A, Rubio JP, Rampoldi L, Ho M, Dobson-Stone C, Tison F, Symmans WA, Oechsner M, Kalckreuth W, Watt JM, Corbett AJ, Hamdalla HHM, Marshall AG, Sutton I, Dotti MT, Malandrini A, Walker RH, Daniels G, Monaco AP. 2001. McLeod neuroacanthocytosis: Genotype and phenotype. Annals of Neurology 50: 755–764. PubMed ID: 11761473
  • Ho M, Chelly J, Carter N, Danek A, Crocker P, Monaco AP. 1994. Isolation of the gene for McLeod syndrome that encodes a novel membrane transport protein. Cell 77: 869–880. PubMed ID: 8004674
  • Ho MF, Chalmers RM, Davis MB, Harding AE, Monaco AP. 1996. A novel point mutation in the McLeod syndrome gene in neuroacanthocytosis. Annals of neurology 39: 672–675. PubMed ID: 8619554
  • Jung HH, Danek A, Walker RH, Frey BM, Gassner C. 2004. McLeod Neuroacanthocytosis Syndrome. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301528
  • Jung HH, Danek A, Walker RH. 2011. Neuroacanthocytosis syndromes. Orphanet J Rare Dis 6: 68. PubMed ID: 22027213
  • Peng J, Redman CM, Wu X, Song X, Walker RH, Westhoff CM, Lee S. 2007. Insights into extensive deletions around the XK locus associated with McLeod phenotype and characterization of two novel cases. Gene 392: 142–150. PubMed ID: 17300882
  • Stanfield GM, Horvitz HR. 2000. The ced-8 Gene Controls the Timing of Programmed Cell Deaths in C. elegans. Molecular cell 5: 423–433. PubMed ID: 10882128

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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