General information: The SALSA MLPA Probemix P104 Menkes ATP7A is a research use only (RUO) assay for the detection of deletions or duplications in the ATP7A gene, which is associated with Menkes disease (MD).

Menkes disease (MD) is a multi-systemic disorder of copper metabolism. Progressive neurodegeneration and connective tissue disturbances, together with the peculiar ‘kinky’ hair are the main manifestations. MD is an X-linked recessive disorder, and as expected the vast majority of patients are males. MD occurs due to pathogenic variants in the ATP7A gene and the vast majority of ATP7A pathogenic variants are intragenic mutations or partial gene deletions. ATP7A is an energy dependent transmembrane protein, which is involved in delivery of copper to the copper-dependent enzymes and is therefore critical for copper homeostasis. Severely affected MD patients usually die before the third year of life.

The ATP7A gene (23 exons) spans ~140 kb of genomic DNA and is located on chromosome Xq21.1, ~78 Mb from the p-telomere.

More information is available at https://www.ncbi.nlm.nih.gov/books/NBK1413/.

Probemix content: The SALSA MLPA Probemix P104-C2 Menkes ATP7A contains 34 MLPA probes with amplification products between 130 and 445 nucleotides (nt). This includes one probe for each exon of the ATP7A gene and two probes for exon 1. In addition, 10 reference probes are included that detect locations on the X-chromosome. 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 (see table below). 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.