POL III Leukodystrophies
Also known as: 4H syndrome, hypomyelinating leukodystrophy with or without hypodontia and/or Hypogonadotropic hypogonadism: HLD7 and HLD8
Gene: POLR3A
Protein: DNA-directed RNA polymerase III subunit RPC1
Gene: POLR3B
Protein: DNA-directed RNA polymerase III subunit RPC2
Clinical Characteristics
- Cerebellar signs:
- Progressive ataxia
- Intention tremor
- Dysarthria, dysmetria, dysdiadochokinesis
- Progressive upper motor neuron dysfunction:
- Spasticity
- Mild hyperreflexia
- MRI findings:
- Hypomyelination
- Cerebellar atrophy
- Hypoplastic corpus callosum
- Childhood or juvenile onset (reported ages range from 1–20 years)
- Extrapyramidal dysfunction such as dystonia
- Dental abnormalities (delayed dentition, hypodontia, etc.)
- Hypogonadotropic hypogonadism
- Eye movement abnormalities and myopia
- Mild to moderate intellectual disability with or without cognitive regression
- Sensory deficits:
- Sensorineural hearing loss
- Myopia
- Optic atrophy
- Inter- and intra-familial variability
Inheritance pattern: Autosomal recessive for both POLR3A and POLR3B
What Can Be Learned From This Test
Testing is performed by sequencing the entire coding region of POLR3A and POLR3B. This will detect point mutations, small deletions and small insertions. It will not detect a partial or whole gene deletion or duplication. A negative test result does not rule out a genetic cause of hypomyelinating leukodystrophy, since there are many other genes associated with leukodystrophies, some of which are available for testing in our lab.
Sequencing of POLR3A with reflex to sequencing of POLR3B is recommended, however, testing can be done concurrently or in any order specified.
Sample Requirements
Draw 2ml–4ml of blood in EDTA/purple-top tube (minimum of 1ml–2ml for infants).
Turnaround time: 10-14 business days per gene
CPT Codes and Cost
Full Gene Sequencing
POLR3A
- Code: 81479
- Cost: $1,700
POLR3B
- Code: 81479
- Cost: $1,700
Known Variant Testing
- Code: 81479
- Cost: $225