Lab Dept:

Anatomic Pathology

Test Name:


General Information

Lab Order Codes:



Von Recklinghausen disease; Legius Syndrome (SPRED1)

CPT Codes:

Combinations of the following codes will be billed based on findings: 81408 – NF1 Sequencing
81407 – NF1 Deletion/Duplication
88230 – Tissue culture for non-neoplastic disorders; lymphocyte
81479 – NF1 Microsatellite Analysis
81405 – SPRED1 Sequencing
81404 – SPRED1 Deletion/Duplication

Test Includes:

Sequencing of the NF1 and SPRED1 genes, including Deletion/Duplicaton when appropriate.


Test Indications:

NF1 is characterized by multiple café-au-lait spots, Lisch nodules and cutaneous neurofibromas. Other complications such as plexiform neurofibromas, learning disabilities, seizures and malignancies may occur. The phenotype of NF1 is variable both within and between families. Patients with deletions of the entire gene typically have a more severe presentation including dysmorphic facial features, early onset and large number of neurofibroma and mental retardation. NF1 is an autosomal dominant disorder with a very high rate of new mutations.

A new autosomal dominant condition (SPRED1 – Legius Syndrome) resembling NF1 was described, consisting of mainly multiple CAL-spots, freckling and relative macrocephaly. In addition, patients will receive simultaneous comprehensive SPRED1 along with NF1 analysis. A direct test based on a gDNA based core assay resulting in the full characterization of the SPRED1 mutation. The complete SPRED1 coding region is analyzed by sequencing exons 1 to 7 starting from the sample submitted for NF1 testing. In addition, DNA copy number analysis by MLPA is performed. Mutations screened for include truncating mutations (nonsense, frameshift, splicing mutations), missense mutations, multi-exon deletions or duplications and total gene deletions.

Lab Testing Sections:

Anatomic Pathology - Sendouts

Referred to:

University of Alabama Medical Genomic Laboratory (NF1 Test 1 Comprehensive)

Phone Numbers:

MIN Lab: 612-813-6280

STP Lab: 651-220-6550

Test Availability:

Sunday – Thursday

Turnaround Time:

5 – 6 weeks

Special Instructions:

Restricted draw times, see Test availability. A completed requisition form and informed consent with a phenotypic checklist must accompany each sample. For questions regarding the forms, please call 1-800-499-4363.


Specimen Type:

Whole blood


Lavender (EDTA) top tube

Draw Volume:

10 mL EDTA (Minimum pediatric: 3 mL) whole blood

Processed Volume:

Same as Draw Volume


Routine venipuncture. Invert sample gently to mix. Forward immediately to the lab.

Special Processing:

Lab Staff: Do Not centrifuge. Specimen must remain in original collection container. Ship specimen ASAP, with proper forms, at ambient temperature via overnight courier. Blood must reach the U of Alabama within 60 hours of draw.

Patient Preparation:


Sample Rejection:

Samples greater than 60 hours old, mislabeled or unlabeled specimens, specimens missing paperwork


Reference Range:

No mutations detected

Critical Values:



Germline mutations in the NF1 gene have been identified in >95% of patients (with sporadic disease as well as those with a positive family history).


Phytohemagglutinin-stimulated lymphocyte culture, Microsatellite analysis, Protein truncation test (PTT), cycle sequencing and long-range RT-PCR, and MLPA when indicated.


University of Alabama Medical Genomics Laboratory January 2013
(800) 499-4363 Fax (205) 996-2929