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Megalencephalic Leukoencephalopathy with Subcortical Cysts via the MLC1 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
MLC1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7161MLC181479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

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

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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.


Genetic Counselors


  • Renee Bend, PhD

Clinical Features and Genetics

Clinical Features

Megalencephalic leukoencephalopathy with subcortical cysts (MLC, OMIM 604004), also known as Van der Knaap disease is a slowly progressive myelinopathy characterized by macrocephaly, delay in walking, early-onset ataxia, seizure, and spasticity. Motor dysfunction, mild mental retardation, and behavioral problems may occur later in life. Additional late-onset symptoms include cerebellar ataxia, hypertonia, dysarthria, and dysphagia. Hallmark magnetic resonance imaging (MRI) findings include subcortical cysts in the tips of the temporal lobes and in frontoparietal subcortical areas and swollen cerebral white matter. Onset of symptoms usually occurs during the first year of life (Van der Knaap et al. Ann Neurol 37:324-334, 1995). MLC is clinically heterogeneous with regards to age of onset, degree of macrocephaly and mental impairment, severity, and disease progression. MLC is a rare disease that affects patients worldwide. Incidence is higher than expected within consanguineous populations (Topcu et al. Brain Dev 20:142-153, 1998).


MLC is usually inherited in an autosomal recessive manner. Defects in two genes, MLC1 and HEPACAM, have been reported in patients with MLC (Leegwater et al. Am J Hum Genet 68:831-838, 2001; López-Hernández et al. Am J Hum Genet 88:422-32, 2011). Variants in MLC1 account for ~75% of patients with a clinical diagnosis and MRI findings of MLC (Boor et al. Hum Mutat 27:505-512, 2006). Over 80 different pathogenic variants have been reported to date and include most types. Gross deletions account for ~ 6% of all MLC1 variants, while nonsense variants appear to be rare. Variants have been reported in patients from various ethnic populations. Several variants are prevalent in specific populations. These include two missense variants, p.Gly59Glu and p.Ser93Leu, that are common in the Libyan Jewish and Japanese populations, respectively. A founder variant, c.135insC (p.Cys46LeufsX34), has been documented in East-Indian populations. However, no genotype-phenotype correlations have been established because of the clinical variability among patients with the same MLC1 variants. The MLC1 protein is expressed mainly in the brain and leukocytes and has a putative transport function (Boor et al. J Neuropathol Exp Neurol 64:412-419, 2005).

Clinical Sensitivity - Sequencing with CNV PG-Select

This test detects variants in ~ 75% of individuals with MLC.

Testing Strategy

This test provides full coverage of all coding exons of the MLC1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Patients with clinical diagnosis and MRI findings of MLC and potential heterozygous carriers. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in MLC1.


Official Gene Symbol OMIM ID
MLC1 605908
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Megalencephalic Leukoencephalopathy with Subcortical Cysts Panel


  • Boor, P. K., et.al. (2005). "MLC1: a novel protein in distal astroglial processes." J Neuropathol Exp Neurol 64(5): 412-9. PubMed ID: 15892299
  • Ilja Boor, P. K., et.al. (2006). "Megalencephalic leukoencephalopathy with subcortical cysts: an update and extended mutation analysis of MLC1." Hum Mutat 27(6): 505-12. PubMed ID: 16652334
  • Leegwater, P. A., et.al. (2001). "Mutations of MLC1 (KIAA0027), encoding a putative membrane protein, cause megalencephalic leukoencephalopathy with subcortical cysts." Am J Hum Genet 68(4): 831-8. PubMed ID: 11254442
  • Lopez-Hernandez, T., et.al. (2011). "Mutant GlialCAM causes megalencephalic leukoencephalopathy with subcortical cysts, benign familial macrocephaly, and macrocephaly with retardation and autism." Am J Hum Genet 88(4): 422-32. PubMed ID: 21419380
  • Topcu, M., et.al. (1998). "Megalencephaly and leukodystrophy with mild clinical course: a report on 12 new cases." Brain Dev 20(3): 142-53. PubMed ID: 9628190
  • van der Knaap, M. S., et.al. (1995). "Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children." Ann Neurol 37(3): 324-34. PubMed ID: 7695231


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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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