General information
The SALSA MLPA
Probemix P107 Neurometabolic disorders is a
research use only (RUO) assay for the detection of deletions or duplications in the D
2HGDH,
L2HGDH,
MLYCD and
MLC1 genes, which are associated with neurometabolic disorders.
The
D2HGDH gene encodes D-2-hydroxyglutarate dehydrogenase, a mitochondrial enzyme belonging to the FAD-binding oxidoreductase/transferase type 4 family. This enzyme converts D-2-hydroxyglutarate to 2-ketoglutarate. Mutations in the
D2HGDH gene are present in D-2-hydroxyglutaric aciduria, a rare recessive neurometabolic disorder causing developmental delay, epilepsy, hypotonia, and dysmorphic features.
The
L2HGDH gene encodes L-2-hydroxyglutarate dehydrogenase, an FAD-dependent enzyme that oxidizes L-2-hydroxyglutarate to alpha-ketoglutarate in a variety of mammalian tissues. Mutations in this gene cause L-2-hydroxyglutaric aciduria, a rare autosomal recessive neurometabolic disorder resulting in moderate to severe intellectual disability.
Malonyl-CoA decarboxylase deficiency is a rare autosomal recessive (liver, brain, heart, and skeletal muscle) metabolic disorder characterized by malonic aciduria, developmental delay, seizures, hypoglycemia, acidosis, short stature and cardiomyopathy. The disorder is caused by mutations in the malonyl-CoA decarboxylase gene (
MLYCD).
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an inherited neurological disorder with macrocephaly before the age of one and slowly progressive deterioration of motor functions. Mutations in the
MLC1 gene, encoding a putative membrane protein, have been identified as a cause for MLC.
The
D2HGDH gene (10 exons), spans ~34 kb of genomic DNA and is located on 2q37.3, ~242 Mb from the p-telomere (close to the q-telomere). The
L2HGDH gene (10 exons), spans ~70 kb of genomic DNA and is located on 14q22.1, ~50 Mb from the p-telomere. The
MLYCD gene (5 exons), spans ~28 kb of genomic DNA and is located on 16q23.3, ~82 Mb from the p-telomere. The
MLC1 gene (12 exons), spans ~26 kb of genomic DNA and is located on 22q13.33, ~49 Mb from the p-telomere.
More information is available at
https://www.ncbi.nlm.nih.gov/books/NBK1535/.
This SALSA MLPA probemix is not CE/FDA registered for use in diagnostic procedures. Purchase of this product includes a limited license for research purposes.
Probemix content
The SALSA MLPA Probemix P107-B3 Neurometabolic disorders contains 44 MLPA probes with amplification products between 130 and 481 nucleotides (nt). This includes five probes for the
D2HGDH gene, ten probes for the
L2HGDH gene, five probes for the
MLYCD gene and 12 probes for the
MLC1 gene. In addition, 12 reference probes are included that detect autosomal chromosomal locations. Complete probe sequences and the identity of the genes detected by the reference probes are available online (
www.mrcholland.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.mrcholland.com.