Genotype to Phenotype

There really hasn’t been a good attempt to date at trying to correlate COMP mutation with disease phenotype (ie MED and/or PSACH. This became particularly obvious with our recent revision of the MED and PSACH GeneReview articles, when the editors asked us if there have been on progress on genotype to phenotype correlations.

To address this omission we collated 300 mutations that have either already been published or were identified as part of the Manchester diagnostic service and attempted to correlate COMP mutation with disease phenotypes. The figure below shows this grouping of mutations and identifies specific regions of COMP that are mutation-disease specific:-


An illustration of the type III repeat region of COMP and the location of missense mutations and in-frame deletions, insertions or indels that lead to PSACH and/or MED.

Each of the 8 type III repeats are indicated on the left (T31, T32 etc.) along with the number of the COMP residue at the start of each repeat. The N- and C-type motifs are shown at the top and the residues that comprise each motif are boxed. The consensus sequence for the N- and C-type motifs are shown below.

Residues that have missense mutations which cause MED are coloured GREEN, those that cause PSACH are coloured RED and mutations reported to cause both PSACH and MED are coloured BLUE. In-frame deletions, insertions or indels are double underlined using the same PSACH-MED colour scheme. The number of patients with a missense mutation identified at each codon is indicated above the relevant residue. Missense mutations in blocks of COMP residues that cause MED are highlighted in blue and those that cause PSACH are highlighted in green.

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