NEUROFIBROMATOSIS TYPE 1 (NF1)
FISH ANALYSIS

The Kleberg Cytogenetics Laboratory offers a fluorescence in situ hybridization (FISH)-based assay for identifying the microdeletion in the NF1 gene (17q11.2) associated with the severe manifestation of neurofibromatosis type I (NF1).

Clinical Features:

NF I 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 neurofibromas and mental retardation. NF1 is an autosomal dominant disorder with a very high rate of new mutations.

Reasons for Referral:

Patients with a clinical diagnosis of NF1 who present with a more severe phenotype, as described above, may be tested for microdeletions of NF1 by FISH. If an affected individual has been found to have a deletion, FISH studies are then indicated on the parents and other family members with a suspected diagnosis. Prenatal diagnosis may be performed if an affected family member has been studied in our laboratory and shown to have a deletion detectable by FISH. Please call regarding all prenatal samples.

Testing Methodology:

FISH is the application of fluorescently labeled DNA molecules to metaphase chromosomes and interphase nuclei for the detection of chromosome abnormalities and alterations. It is a rapid, reliable and direct approach for identifying patients with microdeletions or microduplications. FISH analysis for NF1 is performed on metaphase chromosomes. The presence of a single hybridization signal indicates a deletion. Deletions of the NF1 gene occur in approximately 5% of all patients with NF1. In patients with a severe phenotype, deletions may be detected in approximately 20%. The majority of patients with NF1 have other mutations in the NF1 gene not detected with this FISH assay.

Specimen Requirements:

Whole blood in sodium heparin (green-top) tubes:
Newborn (< 3 months): Minimum 0.5 -2.0 CC
Adult/Child: Minimum 3.0 -5.0 CC

Shipping and Handling:

All tubes must be labeled with the patient's testname and date of birth, and a completed requisition form must accompany each sample. If the laboratory is billing the patient's insurance, please enclose a copy of the insurance card. Ship specimens for overnight delivery at ambient temperature. Please notify the laboratory of incoming samples.

Turnaround Time:

7-10 days

CPT Codes and Prices:

88230, 88273, 88271, 88291

References:

1. Wu, et al. (1995) Am. J. Med. Genet. 59: 528-535.
2. Tonsgard, et al. (1997) Am. J. Med. Genet. 73: 80-86.
3. Riva, et al. (2000) Am. J. Hum. Genet. 66: 100-109.
4. Kluwe, et al. (2004) Hum. Mutat. 23: 111-116.

Forms:

>> Cytogenetics Requisition
>> Prenatal Requisition

Test Code:

8474