General information
The SALSA MLPA Probemix P257 TERT-DKC1 is a
research use only (RUO) assay for the detection of deletions or duplications in the
DKC1,
TERT and
TERC genes, which are associated with dyskeratosis congenita.
Dyskeratosis congenita (DC) is characterised by multiple features including mucocutaneous abnormalities, bone marrow failure and an increased predisposition to cancer (Dokal 2011). While DC exhibits marked clinical and genetic heterogeneity, the wide range of disease manifestations caused by this syndrome have a defective telomere maintenance in common. DC is caused by mutations is several genes, three of which are covered by the P257 TERT-DKC1 probemix, with the mode of inheritance varying by gene. X-linked recessive DC (~25% of DC) is characterized by mutations in the
DKC1 gene (Dokal et al. 2015), which encodes dyskerin, a component of H/ACA small nucleolar ribonucleoprotein (snoRNP) particles (Dokal 2011). Mutations in
TERC, the RNA component, and
TERT, the enzymatic component of telomerase, each constitute ~5% of all DC cases (Dokal et al. 2015). Whereas
TERC mutations lead to autosomal dominant DC,
TERT mutations can lead to either autosomal dominant or autosomal recessive DC. DC has a prevalence of 1 in a million, and 90% of all mutations leading to this syndrome come from single nucleotide variants, although deletions (4.8%) and duplications (2%) have also been observed (AlSabbagh 2020).
More information is available at
https://www.ncbi.nlm.nih.gov/books/NBK22301/.
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 P257-A3 TERT-DKC1 contains 47 MLPA probes with amplification products between 130 and 490 nucleotides (nt). This includes at least one probe for each of the 15 exons of the
DKC1 gene. This probemix also contains at least one probe for each exon of the
TERT gene, with the exception of exon 1. Finally, two probes for the single
TERC exon and two probes flanking the
TERC gene are present. In addition, eleven 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.