Gene: LMNB1
Protein: lamin-B1
Clinical characteristics:
- Slowly progressive neurologic disorder
- Onset in fourth or fifth decade of life
- Symmetric demyelination of the central nervous system
- Phenotype similar to chronic progressive multiple sclerosis
- Lack of astrogliosis and preservation of oligodendria (in contrast to multiple sclerosis)
- Autonomic dysfunction (typically precedes neurological symptoms)
- Orthostatic hypotension
- Abnormal bowel and bladder regulation
- Impotence in males
- Decreased sweating
- Loss of fine motor skills
- Progressive spasticity
- Nystagmus
- Ataxia
Inheritance pattern: Autosomal dominant
What this test can tell us:
Testing is performed by quantitative multiplex PCR to look for a duplication of LMNB1. Fluorescent primers are used to amplify select exons of the LMNB1 gene, along with several reference genes. The PLP1 gene is included (see Pelizaeus-Merzbacher disease). The quantity of each PCR product is determined by measuring the intensity of the fluorescence. Copy number is calculated based on the normalized ratio of the LMNB1 gene to each of the reference genes for the patient and controls.
This test will detect duplications of LMNB1. It will not detect point mutations or smaller deletions or insertions. LMNB1 is the only gene known to be associated with adult onset autosomal dominant leukodystrophy (ADLD). To date (Jan. 2011), duplications of the gene have been the only mutations identified in association with ADLD.
A negative test does not rule out a genetic cause of a neurologic disorder. There are many other genes associated with different types of neurologic disorders and leukodystrophies. Testing for some of the genes associated with leukodystrophies of childhood onset is available in our laboratory and can be performed if clinically indicated.
Sample requirements: Draw one or two 4-cc tubes of blood in EDTA/purple-top tube (minimum of 1-2 cc for infants).
Turn around time: 4 – 6 weeks
CPT codes and cost: 83891 x 1 83900 x 1 83909 x 1 83912 x 1 $330