General information
The SALSA MLPA
Probemix P444 COL4A4 is a
research use only (RUO) assay for the detection of deletions or duplications in the
COL4A4 gene which is associated with Alport syndrome.
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 et al. 2019).
Although point mutations in
COL4A4 may be a more common cause of disease, intragenic deletions of
COL4A4 have been reported (Morinière et al. 2014).
More information is available at
https://www.ncbi.nlm.nih.gov/books/NBK1207/
Probemix content
The SALSA MLPA Probemix P444-A3 COL4A4 contains 43 MLPA probes with amplification products between 130 and 510 nucleotides (nt). This includes 35 probes for the
COL4A4 gene. In addition, eight 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.