Autosomal Dominant Leukodystrophy, Adult Onset
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 Can Be Learned From This Test
Adult onset autosomal dominant leukodystrophy (ADLD) is caused by a duplication of the LMNB1 gene. One family has been reported in which a large deletion upstream of the LMNB1 gene resulted in ADLD due to overexpression of the lamin-B1 protein.
Testing is offered in tiers and can be performed either sequentially or simultaneously. Testing is performed by quantitative multiplex PCR to look for a duplication of LMNB1 or the upstream deletion. Fluorescent primers are used to amplify select exons of the LMNB1 gene or the relevant upstream region, along with several reference genes.
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 targeted regions to each of the reference genes for the patient and controls.
These tests will detect duplications of LMNB1 or the upstream deletion. They 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 (2022), sequence variants of LMNB1 are not known to be associated with adult onset autosomal dominant leukodystrophy (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 lab and can be performed if clinically indicated.
Sample Requirements
Draw 2ml–4ml of blood in EDTA/purple-top tube (minimum of 1ml–2ml for infants).
Turnaround time: 10-14 business days
CPT Codes and Cost
Tier 1: Gene Duplication
- Code: 81479
- Cost: $350
Tier 2: Upstream Deletion Testing
- Code: 81479
- Cost: $450
Known Variant Testing
- Code: 81479
- Cost: $350