L1 Syndrome via the L1CAM Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
304 L1CAM$1220.00 81407 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity
Sensitivity of this test is currently unknown.

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 L1CAM$990.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Features
L1 syndrome is a neurological disorder characterized by hydrocephalus, mental retardation, spasticity of the lower limbs and adducted thumbs. The clinical spectrum of L1 syndrome involves X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS; OMIM 307000), MASA syndrome [an acronym for mental retardation, aphasia, spastic paraplegia, adducted thumbs; OMIM 303350], spastic paraplegia type 1 (SPG1; OMIM 303350), X-linked complicated corpus callosum agenesis (OMIM 304100) (Rosenthal et al. Nat Genet 2:107-112, 1992; Jouet et al. Nat Genet 7:402-407, 1994; Fransen et al. Hum Mol Genet 6:1625-1632, 1997) and CRASH syndrome [acronym for corpus callosum hypoplasia, retardation, aphasia, spastic paraplegia and hydrocephalus] (Rosenthal et al. 1992; Jouet et al. 1994; Vits et al. Nat Genet 7:408-413, 1994; Fransen et al. 1997; Weller et al. Hum Mutat 18:1–12, 2001).  Males with HSAS are born with severe hydrocephalus, adducted thumbs, spasticity and severe mental retardation. In less severe cases, affected males may only demonstrate developmental delay and mild to moderate mental retardation. Furthermore, intra- and interfamily phenotypic variations have also been reported (Finckh et al. Am J Med Genet 92:40-46, 2000). Of note, bilateral absence of the pyramids detected by MRI or autopsy is an almost pathognomonic finding for L1 syndrome (Chow et al. Acta Neuropathol 65:313-317, 1985).
L1 syndrome is inherited as an X-linked recessive manner and is caused by mutations in the L1CAM gene. L1CAM encodes a neuronal cell adhesion molecule (L1). L1 is an axonal glycoprotein, which consists of a large extracellular part possessing six immunoglobulin-like and five fibronectin-repeats (type III) domains, which is linked via a single transmembrane sequence to a conserved short intracellular cytoplasmic domain. L1 plays an important role in nervous system development, including neuronal migration and differentiation, axon growth and synapse formation (Schmid et al. Curr Opin Neurobiol 18:245-250, 2008). A mix of missense, nonsense, frameshift and splicing mutations as well as gross deletion and duplication mutations have been reported in L1CAM (Rosenthal et al. Nat Genet 2:107-112, 1992; Jouet et al. Nat Genet 7:402-407, 1994; Vits et al. Nat Genet 7:408-413, 1994; Bott et al. Am J Med Genet 130A:84-87, 2004; Van Camp et al. Nat Genet 4:421-425, 1993; Vos et al. Hum Mut 31:E1102-E1109, 2010).
Testing Strategy
This test involves bidirectional sequencing using genomic DNA of all 28 coding exons (exon 1-28) of the L1CAM gene plus ~10 bp of flanking non-coding DNA on each side. We will also sequence and single exon (Test #100) in family members of patients with a known mutation or to confirm research results.
Indications for Test
Candidates for this test are males with symptoms consistent with L1 syndrome and family members of patients who have known L1CAM mutations.


Official Gene Symbol OMIM ID
L1CAM 308840
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Genetic Counselors
  • Bott, L., (2004). "Congenital idiopathic intestinal pseudo-obstruction and hydrocephalus with stenosis of the aqueduct of sylvius." Am J Med Genet A 130A(1): 84-7. PubMed ID: 15368500
  • Chow, C. W., (1985). "Congenital absence of pyramids and its significance in genetic diseases." Acta Neuropathol 65(3-4): 313-7. PubMed ID: 3976367
  • Finckh, U., (2000). "Spectrum and detection rate of L1CAM mutations in isolated and familial cases with clinically suspected L1-disease." Am J Med Genet 92(1): 40-6. PubMed ID: 10797421
  • Fransen, E., (1997). "L1-associated diseases: clinical geneticists divide, molecular geneticists unite." Hum Mol Genet 6(10): 1625-32. PubMed ID: 9300653
  • Jouet, M., (1994). "X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene." Nat Genet 7(3): 402-7. PubMed ID: 7920659
  • Rosenthal, A., (1992). "Aberrant splicing of neural cell adhesion molecule L1 mRNA in a family with X-linked hydrocephalus." Nat Genet 2(2): 107-12. PubMed ID: 1303258
  • Schmid, R. S., Maness, P. F. (2008). "L1 and NCAM adhesion molecules as signaling coreceptors in neuronal migration and process outgrowth." Curr Opin Neurobiol 18(3): 245-50. PubMed ID: 18760361
  • Van Camp, G., (1993). "A duplication in the L1CAM gene associated with X-linked hydrocephalus." Nat Genet 4(4): 421-5. PubMed ID: 8401593
  • Vits, L., (1994). "MASA syndrome is due to mutations in the neural cell adhesion gene L1CAM." Nat Genet 7(3): 408-13. PubMed ID: 7920660
  • Vos, Y. J., Hofstra, R. M. (2010). "An updated and upgraded L1CAM mutation database." Hum Mutat 31(1): E1102-9. PubMed ID: 19953645
  • Weller, S., Gartner, J. (2001). "Genetic and clinical aspects of X-linked hydrocephalus (L1 disease): Mutations in the L1CAM gene." Hum Mutat 18(1): 1-12. PubMed ID: 11438988
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

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Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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