HUM-MOLGEN DIAGnostics/Clinical Research


Reply to Ricky Lewis: inv7 and OI

In reply to Rick Lewis' request on the risk of OI or EDS VII in a carrier of 46 XY inv(7)q21-q22 , I can offer the following comments:

1. It is correct that COL1A2 maps in that area.

2. If the gene were interrupted by the inversion, you might expect a mild or even asymptomatic form of OI, as truncated chains would most probably NOT participate in collagen trimer formation ( = null allele of COL1A2 has no or minimal clinical consequences).

3. If I remember well (but I have no time to check the paper - was it a Alex Knisely case?), the reported case of severe OI with such an inversion had to be explained as "that inversion PLUS a structural mutation on the other chromosome". I would check for that.

4. EDS type VIIB is equally highly unlikely. That is caused by exon 6 skipping mutations only, not likely to be produced by a break through the gene.

5. IF the COL1A2 gene were indeed interrupted by the inversion, the proband would have to rely on an intact gene on the other chromosome. A mutation in the other gene might indeed be deleterious.

6. I would not worry with OI - especially if good ultrasound (at what gestational week?) is normal.

7. Perhaps one should worry about other consequences - often, inversions which appear to be balanced do have clinical consequences - mental retardation or so. Check the parents, it would be very nice to find the same in one parent.

Good luck and best regards. Please do let us know the outcome.

PD Dr. A. Superti-Furga
Division of Metabolic and Molecular Diseases
Department of Pediatrics
University of Zurich
CH-8032 Zurich,
Phone +41-1-266-7722
FAX +41-1-266-7167