Defects in COL11A1 gene cause Marshall and type II Stickler syndromes. Marshall syndrome is an autosomal dominant inherited disease characterised by short stature, nearsightedness, hearing loss and intracranial ossifications. Type II Stickler syndrome patients have similar symptoms but are of near normal height and exhibit no bony overgrowths. Both syndromes occasionally present with cleft palate and patients frequently develop early osteoarthritis (Kahler et al., 2008). Since the characteristics of these syndromes overlap, it has been argued whether they are distinct entities or different manifestations of a single syndrome.

The COL11A1 gene (67 exons) spans ~232 kb of genomic DNA and is located on 1p21.1, 103 Mb from p-telomere. These P381-A3 / P382-A3 COL11A1 probemixes contain probes for 56 of the 67 exons. No probes are present for exons 12, 13, 23, 31, 32, 45, 47, 50, 52, 55 and 65. Furthermore, the P381-A3 contains 11 reference probes and the P382-A3 contains 10 reference probes, detecting different autosomal chromosomal regions.

This SALSA^® MLPA^® probemix is designed to detect deletions/duplications of one or more sequences in the aforementioned gene in a DNA sample. Heterozygous deletions of recognition sequences should give a 35-50% reduced relative peak height of the amplification product of that probe. Note that a mutation or polymorphism in the sequence detected by a probe can also cause a reduction in relative peak height, even when not located exactly on the ligation site! In addition, some probe signals are more sensitive to sample purity and small changes in experimental conditions. Therefore, deletions and duplications detected by MLPA should always be confirmed by other methods. Not all deletions and duplications detected by MLPA will be pathogenic; users should always verify the latest scientific literature when interpreting their findings. We have no information on what percentage of defects in these genes is caused by deletions/duplications of complete exons. Finally, note that most defects in this gene are expected to be small (point) mutations which will not be detected by this SALSA^® MLPA^® test.