Menkes Disease and Hereditary Motor Neuropathy via the ATP7A Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
4883 ATP7A 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4883ATP7A81479 81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

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

Menkes disease (MNK, OMIM 309400) is an X-linked multisystemic disorder of copper metabolism. Three variants of MNK are recognized.

1) Classic MNK is the most common and most severe variant. It is characterized by kinky hair, pili torti, hypopigmentation, loose skin, failure to thrive, progressive neurodegeneration, and loss of previously developed skills. Symptoms begin in infancy and death occurs in early childhood.

2) Intermediate MNK is characterized by mild development delay, cerebellar ataxia, later onset, and longer survival (Danks et al. Am J Med Genet 30:859-864, 1988).

3) Occipital horn syndrome (OHS, OMIM 304150) is the mildest variant with survival into adulthood. It is distinguished by occipital exostoses on radiographs. OHS is mainly a connective-tissue disorder. Symptoms include recurrent bladder rupture, cutis laxa, and musculoskeletal abnormalities (Lazoff Birth Defects 11:71-74, 1975). To date, MNK disease has been reported in eight female patients (Sirleto et al. Pediatr Res 65:347-351, 2009).

ATP7A-related distal hereditary motor neuropathy (HMN, OMIM 300489) is clinically heterogeneous. Typical features include distal wasting and weakness, reduced compound muscle action potential with decreased motor conduction velocity, minimal or no sensory involvement, and X-linked inheritance (Kennerson et al. Am J Hum Genet 86:343-352, 2010).

Genetics

All variants of MNK disease result from variants in the ATP7A gene, located on the X chromosome (Vulpe et al. Nat Genet 3:7-13, 1993; Chelly et al. Nat Genet 3:14-19, 1993; Das et al. Am J Hum Genet 56:570-576, 1995). Over 170 ATP7A variants have been reported and included most types. Large deletions account for ~ 10% of patients with documented variants (Kaler, GeneReviews, 2010 at www.genetests.org) and appear to result in the classic MNK disease (Tümer et al. Hum Mutat 22:457-464, 2003). However, clear genotype-phenotype correlations have not been established. In addition to MNK disease, two ATP7A missense variants have been recently reported in patients with HMN (Kennerson et al. Am J Hum Genet 86:343-352, 2010).

Clinical Sensitivity - Sequencing with CNV PG-Select

This test detects variants in about 80% of males affected with MNK and female carriers (Kaler, GeneReviews, 2010).

Testing Strategy

This test provides full coverage of all coding exons of the ATP7A gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

1. Male patients with symptoms suggestive of MNK disease or decreased serum copper and ceruloplasmin levels, as well as female carriers.

2. Male patients with X-linked HMN and female carriers.

Gene

Official Gene Symbol OMIM ID
ATP7A 300011
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Distal Hereditary Motor Neuropathy Panel

Citations

  • Chelly, J., et.al. (1993). "Isolation of a candidate gene for Menkes disease that encodes a potential heavy metal binding protein." Nat Genet 3(1): 14-9. PubMed ID: 8490646
  • Danks, D. M. (1988). "The mild form of Menkes disease: progress report on the original case." Am J Med Genet 30(3): 859-64. PubMed ID: 3189408
  • Das, S., et.al. (1995). "Similar splicing mutations of the Menkes/mottled copper-transporting ATPase gene in occipital horn syndrome and the blotchy mouse." Am J Hum Genet 56(3): 570-6. PubMed ID: 7887410
  • Kaler, Stephen G (2010). "ATP7A-Related Copper Transport Disorders." PubMed ID: 20301586
  • Kennerson, M. L., et.al. (2010). "Missense mutations in the copper transporter gene ATP7A cause X-linked distal hereditary motor neuropathy." Am J Hum Genet 86(3): 343-52. PubMed ID: 20170900
  • Lazoff, S. G., et.al. (1975). "Skeletal dysplasia, occipital horns, diarrhea and obstructive uropathy- a new hereditary syndrome." Birth Defects Orig Artic Ser 11(5): 71-4. PubMed ID: 1218238
  • Sirleto, P., et.al. (2009). "Lyonization effects of the t(X;16) translocation on the phenotypic expression in a rare female with Menkes disease." Pediatr Res 65(3): 347-51. PubMed ID: 19092723
  • Tumer, Z., et.al. (2003). "Screening of 383 unrelated patients affected with Menkes disease and finding of 57 gross deletions in ATP7A." Hum Mutat 22(6): 457-64. PubMed ID: 14635105
  • Vulpe, C., et.al. (1993). "Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase." Nat Genet 3(1): 7-13. PubMed ID: 8490659

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

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