General information
The SALSA MLPA Probemixes P191 X-linked Alport syndrome mix 1 and P192 X-linked Alport syndrome mix 2 are research use only (RUO) assays for the detection of deletions or duplications in the COL4A5 gene, which is associated with X-linked Alport syndrome (XLAS).

Alport syndrome (AS) is an inherited disorder of the basement membrane, resulting in progressive renal failure due to glomerulonephropathy, variable sensorineural hearing loss, and variable ocular anomalies. It is a genetically heterogeneous disorder, with all forms resulting from mutations in the genes encoding the alpha-3 (COL4A3; 2q36.3), alpha-4 (COL4A4; 2q36.3), and alpha-5 (COL4A5; Xq22.3) chains of type IV collagen, which is a major structural component of the basement membrane (Nozu et al. 2019). AS can be divided into X-Linked AS (XLAS), autosomal recessive AS (ARAS), and autosomal dominant AS (ADAS). XLAS is caused by mutations in the COL4A5 gene and accounts for approximately 80% of AS, whereas ARAS and ADAS are caused by mutations in the COL4A3 and COL4A4 genes and account for approximately 15% and 5% of AS,respectively (Nozu K et al. 2019).

The first exon of COL4A5 is located very close to the first exon of the COL4A6 gene which encodes one of the other type IV collagen subunits. The two genes are arranged head-to-head and share a common promoter region. Deletions in the COL4A5 gene that extend into the COL4A6 gene result in Alport syndrome-diffuse leiomyomatosis (AS-DL)(Nozu K et al. 2017, Zhou X et al 2021).

More information is available at https://www.ncbi.nlm.nih.gov/books/NBK1207/

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 P191-B4 X-linked Alport syndrome mix 1 contains 37 MLPA probes with amplification products between 130 and 490 nucleotides (nt). This includes 26 probes for the COL4A5 gene and one probe for the COL4A6 gene. In addition, ten reference probes are included that detect locations on the X-chromosome. The SALSA MLPA Probemix P192-B4 X-linked Alport syndrome mix 2 contains 37 MLPA probes with amplification products between 130 and 444 nt. This includes 25 probes for the COL4A5 gene and two probes for the COL4A6 gene. In addition, ten 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. 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.