General information
The SALSA MLPA Probemix P143 MFN2-MPZ is a research use only (RUO) assay for the detection of deletions or duplications in the MFN2 and MPZ genes, which are associated with Charcot-Marie-Tooth disease type 2A and type 1B, respectively.

Charcot-Marie-Tooth disease constitutes a clinically and genetically heterogeneous group of hereditary motor and sensory neuropathies, affecting approximately 1 in every 2500 individuals. On the basis of electrophysiological criteria, CMT is divided into 2 major types. Type 1, the demyelinating form, is characterised by a slow motor median nerve conduction velocity. Type 2, the axonal form, has normal or slightly reduced nerve conduction velocity.

Mitofusins, such as MFN2, mediate the fusion of mitochondria and thereby contribute to the dynamic balance between fusion and fission that determines mitochondrial morphology. Mutations in the MFN2 gene have been detected in affected members of several families with Charcot-Marie-Tooth disease type 2A (CMT2A).

Myelin protein zero (MPZ) is the major structural protein of peripheral myelin. Mutations in the MPZ gene are associated with the autosomal dominant form of Charcot-Marie-Tooth disease type 1 (CMT1B) which is characterised by progressive slowing of nerve conduction and hypertrophy of Schwann cells. Mutations in MPZ can also produce the more severe polyneuropathies Dejerine-Sottas syndrome (DSS) and congenital hypomyelinating neuropathy (CHN), as well as several types of axonal CMT2.

The MFN2 gene (19 exons) spans ~33 kb of genomic DNA and is located on 1p36.22, 12 Mb from the p-telomere. The MPZ gene (6 exons) spans ~5 kb of genomic DNA and is located on 1q23.3, ~160 Mb from the p-telomere.

More information is available at https://www.ncbi.nlm.nih.gov/books/NBK1358/ and https://www.ncbi.nlm.nih.gov/books/NBK1511/.

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 P143-C3 MFN2-MPZ contains 38 MLPA probes with amplification products between 137 and 427 nucleotides (nt). This includes 20 probes for the MFN2 gene (one probe for each exon and two probes for exon 3) and seven probes for the MPZ gene (one probe for each exon and two probes for exon 1). Two probes upstream of MFN2, targeting the PLOD1 gene, are included. Please note that duplications of PLOD1 exons 10-16 are found in the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA) (Giunta et al. 2005). In addition, nine 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.