General information
The SALSA MLPA Probemix P221 LCA mix-1 is a research use only (RUO) assay for the detection of deletions or duplications in the AIPL1, CRB1, CRX, LCA5 and RPE65 genes, which are associated with Leber congenital amaurosis syndrome.

Leber congenital amaurosis (LCA) syndrome comprises a group of early-onset childhood retinal dystrophies and is characterised by vision loss, nystagmus and severe retinal dysfunction. It is the most common inherited cause of blindness. Pathogenic variants in seventeen genes are known to cause LCA, five of these genes are covered by this probemix.

The AIPL1 gene encodes the aryl hydrocarbon receptor interacting protein-like 1, located in the retinal photoreceptor cells, where it may act as a molecular chaperone. Defects in the AIPL1 gene account for ~4%-8% of all LCA cases. The protein encoded by the CRB1 gene is crumbs family member 1, which plays a role in photoreceptor morphogenesis in the retina. Defects in this gene account for ~10% of all LCA cases. The CRX gene encodes the cone-rod homeobox protein, which regulates retinal photoreceptor cell-specific gene transcription and plays a role in the differentiation of photoreceptor cells. Defects in this gene account for ~3% of all LCA cases. Leber congenital amaurosis 5 protein is encoded by the LCA5 gene, and is involved in centrosomal or ciliary functions. Approximately 1%-2% of all LCA cases are caused by defects in the LCA5 gene. Lastly, the RPE65 gene encodes the retinal pigment epithelium-specific protein 65kDa, which is located in the retinal pigment epithelium where it is involved in the production of 11-cis retinal and in visual pigment regeneration. Defects in RPE65 account for 6%-16% of all LCA cases (Chacon-Camacho and Zenteno 2015).

More information is available at https://www.ncbi.nlm.nih.gov/books/NBK1298/.

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 P221-C2 LCA mix-1 contains 54 MLPA probes with amplification products between 128 and 503 nucleotides (nt). This includes six probes for the AIPL1 gene, nine probes for the LCA5 gene, 13 probes for the CRB1 gene, 14 probes for the RPE65 gene and four probes for the CRX gene. In addition, eight reference probes are included and detect eight 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.