Intended use: The SALSA MLPA probemix P070 Subtelomeres Mix 2B is an in vitro diagnostic (IVD)¹ or a research use only (RUO) assay to detect deletion(s) and/or duplication(s) in subtelomeric regions in human DNA derived from peripheral blood, buccal swab, (un)cultured amniotic fluid obtained in week 16 of the pregnancy or later and free from blood contamination, (un)cultured chorionic villi free from maternal contamination, fetal blood, or products of conception as a potential cause of developmental delay, dysmorphic features, other congenital abnormalities and/or pregnancy loss. Detected abnormalities should always be confirmed by a designated MLPA follow-up probemix or other technique. The results of this test should be interpreted by a clinical molecular geneticist or equivalent.

¹Please 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).

Clinical background: Aberrant copy numbers of subtelomeric regions, e.g. due to an unbalanced translocation, are a frequent cause of developmental delay and congenital abnormalities. This P070-B3 Subtelomeres Mix 2B probemix for MLPA provides a faster, higher-throughput and more economical means than microarray analysis and FISH to identify individuals with a copy number change in one or more subtelomeric regions. MLPA cannot identify balanced rearrangements however, and has a lower detection rate than microarray analysis. Detection rates depend strongly on the patient cohort tested. Examples are 5.9% (Ahn et al. 2007) when testing 455 patients or 3.9% (Stegmann et al. 2008) when testing a patient cohort in which normal G-banding analysis did not detect any abnormalities. Note that the results of Ahn et al. (2007) included some samples containing a genetic anomaly that had been inherited from an unaffected parent and which hence might have been a polymorphism without clinical significance. More information can be found on www.orpha.net and decipher.sanger.ac.uk. See the product description for several publications on probemix P070 Subtelomeres Mix 2B.

Probemix content: SALSA MLPA probemix P070 Subtelomeres Mix 2B contains 46 MLPA probes with amplification products between 132 and 490 nt: two probes for each chromosome. 41 probes are located in subtelomeric regions. No probes are present for the p arms of the 5 acrocentric chromosomes (13, 14, 15, 21, 22). For these, an extra probe is included detecting the q arm, close to the centromere. The subtelomeric probes for chromosome X and Y are identical as they detect sequences in the pseudoautosomal regions (PAR1 and PAR2). More information is present in the product description.

This probemix contains ten quality control fragments generating amplification products between 64 and 121 nt: four DNA Quantity Fragments (Q-fragments), two DNA Denaturation Fragments (D-fragments), one benchmark fragment, and one chromosome X and two chromosome Y-specific fragments. 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.