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HelpTest Code LAB1910 SLC2A1 Single Gene Analysis
Additional Codes
SLC2A1 S+D/D
Clinical System Name
SLC2A1 Single Gene Analysis
Synonyms
GLUT1 Sequencing and Del/Dup
Dystonia 9
Description
This test includes sequencing and CNV analysis for the SLC2A1 gene.
Sample Requirements
Specimen: Whole Blood
Container(s): Lavender Top/EDTA, Yellow/ACD
Preferred Vol: 5.0 mL
Minimum Vol: 3.0 mL (1.0 mL for small infants)
Specimen: DNA
Container(s): Sterile Plastic Tube
Preferred Vol: 5 µg -10 µg of purified DNA at a concentration of at least 100 ng/μL
Alternative Specimen (e.g. salvia or buccal): Alternate Specimen Collection Kits for Genetic Testing
Processing Instructions
Reject due to:
Spin: N
Aliquot: N
Temp: 2 - 8 C
Storage Location: Affix a large Epic label(s) to the tube(s) and place in CPA refrigerator, Send Outs rack.
Off-site Collection: Send whole blood refrigerated.
Stability
| Specimen Type | Temperature | Time |
|---|---|---|
| Whole Blood | Room Temp | 3 d |
| Refrigerated | 7 d | |
| Frozen | Unacceptable | |
| Extracted DNA | Room Temp | 3 - 4 d |
| Refrigerated | 1 y | |
| Frozen | Indefinitely |
Availability
| STAT | TAT |
|---|---|
| N | 3-4 w |
Performing Laboratory
PreventionGenetics
3800 South Business Park Avenue
Marshfield, WI 54449
Phone Number: (715) 387-0484
Department
Department: Send Outs/Genetic
Phone: (206) 987-2563
Reference Range
Interpretive report is provided.
Methodology
NextGen Sequencing
We use a combination of Next Generation Sequencing (NGS) and Sanger sequencing technologies to cover the full coding regions of the listed genes plus ~10 bases of non-coding DNA flanking each exon. As required, genomic DNA is extracted from the patient specimen. For NGS, patient DNA corresponding to these regions is captured using an optimized set of DNA hybridization probes. Captured DNA is sequenced using Illumina’s Reversible Dye Terminator (RDT) platform (Illumina, San Diego, CA, USA). Regions with insufficient coverage by NGS are covered by Sanger sequencing.
For Sanger sequencing, Polymerase Chain Reaction (PCR) is used to amplify targeted regions. After purification of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit. PCR products are resolved by electrophoresis on an ABI 3730xl capillary sequencer. In nearly all cases, cycle sequencing is performed separately in both the forward and reverse directions.
Patient DNA sequence is aligned to the genomic reference sequence for the indicated gene region(s). All differences from the reference sequences (sequence variants) are assigned to one of five interpretation categories, listed below, per ACMG Guidelines (Richards et al. 2015).
(1) Pathogenic Variants
(2) Likely Pathogenic Variants
(3) Variants of Uncertain Significance
(4) Likely Benign Variants
(5) Benign Variants
Human Genome Variation Society (HGVS) recommendations are used to describe sequence variants (http://www.hgvs.org). Rare variants and undocumented variants are nearly always classified as likely benign if there is no indication that they alter protein sequence or disrupt splicing.
Deletion and Duplication Testing via NGS
Copy number variants (CNVs) such as deletions and duplications are detected from next generation sequencing data. We utilize a CNV calling algorithm that compares mean read depth and distribution for each target in the test sample against multiple matched controls. Neighboring target read depth and distribution, and zygosity of any variants within each target region are used to reinforce CNV calls. All CNVs are confirmed using another technology such as PCR, aCGH or MLPA before they are reported.
Clinical Utility
The SLC2A1 gene provides instructions for producing a protein called the glucose transporter protein type 1 (GLUT1). The GLUT1 protein is embedded in the outer membrane surrounding cells, where it transports a simple sugar called glucose into the cells for use as fuel. In the brain, the GLUT1 protein is involved in moving glucose, which is the brain's main energy source, across the blood-brain barrier. The blood-brain barrier acts as a boundary between tiny blood vessels (capillaries) and the surrounding brain tissue; it protects the brain's delicate nerve tissue by preventing many other types of molecules from entering the brain. The GLUT1 protein also moves glucose between cells in the brain called glia, which protect and maintain nerve cells (neurons).
More than 150 SLC2A1 gene pathogenic mutations have been reported in people with GLUT1 deficiency syndrome. This disorder leads to a variety of neurological symptoms that can include developmental delay, intellectual disability, movement problems, and seizures (epilepsy). The mutations that cause GLUT1 deficiency syndrome reduce or eliminate the function of the GLUT1 protein. Having less functional GLUT1 protein reduces the amount of glucose available to brain cells, which affects brain development and function. A diagnosis of GLUT1 deficiency syndrome would allow initiation of treatment with a ketogenic diet that has shown clinical benefit in affected patients.
Dystonia-9, in the dystonia class of disorders which is caused by a mutation in SLC2A1, is an autosomal dominant neurologic disorder characterized by childhood onset of paroxysmal choreoathetosis and progressive spastic paraplegia. Most show some degree of cognitive impairment. Other variable features may include seizures, migraine headaches, and ataxia.
Send Out Instructions
| Reference Test Name: |
GLUT1 Deficiency Syndrome via SLC2A1 Gene |
| Reference Lab Test Code: | 3813 |
| Instructions: | Ship Monday through Friday via FedEx Priority Overnight. Saturday deliveries are accepted. |