General information
The SALSA MLPA
Probemix P493 SMCHD1 is a
research use only (RUO) assay for the detection of deletions or duplications in the
SMCHD1 gene which is associated with Fascioscapulohumeral muscular dystrophy 2 (FSHD2) and Bosma arhinia microphthalmia syndrome (BAMS).
The
SMCHD1 gene (48 exons), spans ~149 kb of genomic DNA and is located on chromosome 18p11.32, ~2.7 Mb from the p-telomere. The
SMCHD1 gene encodes the structural maintenance of chromosomes hinge domain containing protein 1, an epigenetic modifier that plays a role in the regulation of the expression of several genes across the genome. Heterozygous pathogenic
SMCHD1 variants are associated two distinct disorders: FSHD2 and BAMS (Gurzau et al. 2020).
FSHD is form of muscular dystrophy characterised by a distinctive pattern of muscle weakness, starting with the facial, scapular and humeral muscles, later progressing the trunk and lower extremities (Pandya et al. 2008). Two types of FSHD have been described: FSHD1 (>95% of FSHD) and FSHD2 (<5% of FSHD). FSHD1 is caused by a contraction of the D4Z4 repeat array on chromosome 4
in cis with the 4qA haplotype. 80% of FSHD2 cases is caused by a heterozygous
SMCHD1 pathogenic variant, leading to hypomethylation of the D4Z4 repeat array (Zernov and Skoblov 2019).
BAMS is a rare syndrome characterised by among others severe hypoplasia of the nose and eyes, palatal abnormalities and deficient taste and smell (OMIM 603457).
More information on FSHD is available at
https://www.ncbi.nlm.nih.gov/books/NBK1443/
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 P493-A1 SMCHD1 contains 57 MLPA probes with amplification products between 121 and 500 nucleotides (nt). This includes 48 probes for the
SMCHD1 gene. 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.