The SALSA MLPA probemix P138-C1 SLC2A1-STXBP1 is an in vitro diagnostic (IVD)1
or research use only (RUO) assay for (1) the detection of deletions or duplications in the SLC2A1
gene in order to confirm a potential cause and clinical diagnosis for Glucose transporter type 1 deficiency syndrome (GLUT1 DS), and (2) the detection of deletions or duplications in the human STXBP1
gene in order to confirm a potential cause and clinical diagnosis for STXBP1 Encephalopathy with epilepsy (STXBP1-E) and Ohtahara syndrome (OS).This assay is for use with human DNA extracted from peripheral blood.
Deletions or duplications detected with the P138 probemix must be confirmed by another technique. In particular, deletions or duplications detected by only a single probe always require validation by another method. Most defects in the aforementioned genes are point mutations, which will not be detected by MLPA. It is therefore recommended to use this SALSA MLPA probemix in combination with sequence analysis of these genes. This assay is not intended to be used as a standalone assay for clinical decisions. The results of this test must be interpreted by a clinical molecular geneticist or equivalent.
Please note that this probemix is for In Vitro Diagnostic use (IVD) in the countries specified at the end of this product description. In all other countries, the product is for Research Use Only (RUO).
Glucose transporter type 1 (GLUT1) deficiency syndrome (GLUT1 DS; OMIM #606777) is a neurologic disorder with a broad phenotypic variability. GLUT1 DS is usually inherited in an autosomal dominant manner and in very rare cases it can occur as an autosomal recessive disease. About 10% of the autosomal dominant cases have a clinically affected parent, the remaining 90% results from a de novo heterozygous pathogenic variant. The de novo sporadic mutations may also be the result of germline mosaicism in apparently unaffected parents (Takahashi et al. 2017).
The GLUT1 DS phenotype has been reported as classic (~90%) and non-classic (~10%). The classic phenotype is characterized by infantile-onset seizures (usually between 1-6 months), delayed neurologic development, dysarthria, acquired microcephaly, and movement disorders (ataxia, dystonia, chorea). The non-classic phenotype is milder and is characterized by absence of clinical seizures, and frequent paroxysmal dyskinesias (intermittent ataxia, choreoathetosis, dystonia, alternating hemiplegia). More information is available at https://www.ncbi.nlm.nih.gov/books/NBK1430/
STXBP1 Encephalopathy with epilepsy (STXBP1-E), also known as STXBP1 Encephalopathy or Early infantile epileptic encephalopathy-4 (EIEE4; OMIM #612164), belongs to the genetically heterogeneous group of early infantile epileptic encephalopathy (EIEE) disorders. STXBP1-E is inherited in an autosomal dominant pattern, with most of the cases being the result of a de novo mutation in the STXBP1 gene and with no history of the disorder in their family. However, these de novo sporadic mutations may also be the result of germline mosaicism in apparently unaffected parents (Saitsu et al. 2011).
STXBP1-E is characterized by recurrent seizures with early-onset (from 1 day to 13 years of age; in 94% of the cases), global development delay (90% of the cases), abnormal brain function and intellectual disability. Electroencephalography (EEG) abnormalities such as burst suppression pattern and hypsarrhythmia were reported in affected individuals. The most common type of seizures is infantile spasms, that consist of involuntary muscles spasms. Several epileptic syndromes have been linked to the STXBP1
gene, such as Ohtahara syndrome (OS; the most common syndrome, with STXBP1
defects being reported in ~20% of OS patients), West syndrome (WS), Lennox-Gastaut syndrome (LGS), Dravet syndrome (not SCN1A
-related), classic Rett syndrome (not MECP2
-related) and atypical Rett syndrome (not CDKL5
-related). OS can develop into WS, this transition is accompanied by changes in the EEG, from suppression burst (OS) to hypsarrhythmia (WS). When progression continues to LGS it develops a generalized slow spike-wave pattern. More information is available at https://www.ncbi.nlm.nih.gov/books/NBK396561/
The P138-C1 SLC2A1-STXBP1 probemix contains 43 MLPA probes with amplification products between 130 and 486 nt. It contains twelve probes for SLC2A1
and twenty-one probes for STXBP1
covering each exon of these genes. In addition, ten reference probes are included in this probemix.The identity of the genes detected by the reference probes is available online (www.mlpa.com
This probemix contains nine quality control fragments generating amplification products between 64 and 105 nt: four DNA Quantity Fragments (Q-fragments), two DNA Denaturation Fragments (D-fragments), one benchmark fragment, and one chromosome X and one chromosome Y-specific fragment. More information on how to interpret observations on these control fragments can be found in the MLPA General Protocol and online at www.mlpa.com