LEUKOENCEPHALOPATHY WITH VANISHING WHITE MATTER
EIF2B5 Sequencing
DNA ANALYSIS

Childhood ataxia with central hypomyelination (CACH)/vanishing white matter (VWM) leukoencephalopathy [OMIM] #603896) is an autosomal-recessive disorder characterized by normal early development and neurologic deterioration in late infancy or early childhood. Juvenile and adult-onset cases have also been described. The neurologic signs include cerebellar ataxia, spasticity, preserved mental function and episodes of rapid deterioration related to febrile infections or head trauma. The MRI is characterized by a diffuse abnormality of the cerebral white matter. The condition is related to mutations in all five subunits of the eukaryotic translation initiation factor (eIF2B). Mammalian eIF2B is a heteropentameric G-protein composed of the five nonidentical subunits α, β, γ, δ, and ε which are encoded by the ubiquitously expressed housekeeping genes EIF2B1, EIF2B2, EIF2B3, EIF2B4 and EIF2B5 respectively. EIF2B5 encodes the ε subunit of the eukaryotic translation initiation factor 2B (eIF2B) and mutations in this gene have been found in multiple patients from different families. Our laboratory offers sequence analysis of the EIF2B5 gene for patients with a clinical diagnosis of vanishing white matter (VWM) leukoencephalopathy.

Reasons for Referral:

Confirmation of clinical diagnosis of leukoencephalopathy with vanishing white matter.
Analysis of at-risk family members for identified mutations. Population carrier screening not offered.
Prenatal diagnosis (Both known mutations only).

Testing Methodology:

Full Sequencing: A PCR-based assay is used to amplify all 16 exons of the EIF2B5 gene. Direct sequencing of amplification products is performed in both the forward and reverse directions using automated fluorescence dideoxy sequencing methods.

Sensitivity:

Clinical: Approximately 60%
Analytical: > 98%

Specimen Requirements:

Blood for DNA: EDTA (purple-top) tubes: Adult/Child: Minimum 6-14 cc
Requisition form must accompany the specimen. Prior to any genetic testing, we recommend genetic counseling and we request that the subject sign our consent statement and submit it with the sample. To receive forms, additional information or specimen collection kits, please contact the laboratory. Please call laboratory for specific requirements for prenatal testing.

Turnaround Time:

Index: 4 weeks
Known Familial Mutation: 3 weeks

CPT Codes and Prices:

Index: 83904X28, 83912, 83909x28, 83898x14, 83894, 83891
Known Familial Mutation: 83904x2, 83912, 83909x2, 83898, 83891, 83894

References:

1. Dietrich J, Lacagnina M, Gass D, Richfield E, Mayer-Proschel M, Noble M, Torres C, Proschel C. (2005)EIF2B5 mutations compromise GFAP+ astrocyte generation in vanishing white matter leukodystrophy. Nat. Med. 11:277-283. Epub 2005 Feb 20.
2. Ohlenbusch A, Henneke M, Brockmann K, Goerg M, Hanefeld F, Kohlschutter A, Gartner J. (2005) Identification of ten novel mutations in patients with eIF2B-related disorders. Hum. Mutat. 25: 411.

Shipping Information

Forms:

>> Gene Sequencing Requisition
>> Prenatal Requisition

Test Codes:

Index: 6210
Known Familial Mutation: 6215
Prenatal (Known Familial Mutation Only): 6220