The authors have no conflicts of interest.
Article first published online: 13 JAN 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 158A, Issue 2, pages 309–314, February 2012
How to Cite
Tompson, S. W., Faqeih, E. A., Ala-Kokko, L., Hecht, J. T., Miki, R., Funari, T., Funari, V. A., Nevarez, L., Krakow, D. and Cohn, D. H. (2012), Dominant and recessive forms of fibrochondrogenesis resulting from mutations at a second locus, COL11A2. Am. J. Med. Genet., 158A: 309–314. doi: 10.1002/ajmg.a.34406
How to Cite this Article: Tompson SW, Faqeih EA, Ala-Kokko L, Hecht JT, Miki R, Funari T, Funari VA, Nevarez L, Krakow D, Cohn DH. 2012. Dominant and recessive forms of fibrochondrogenesis resulting from mutations at a second locus, COL11A2. Am J Med Genet Part A 158A:309–314.
- Issue published online: 19 JAN 2012
- Article first published online: 13 JAN 2012
- Manuscript Accepted: 31 OCT 2011
- Manuscript Received: 17 JUN 2011
- National Institutes of Health. Grant Numbers: DE019567, HD22657, M01-RR00425
- skeletal dysplasia;
Fibrochondrogenesis is a severe, recessively inherited skeletal dysplasia shown to result from mutations in the gene encoding the proα1(XI) chain of type XI collagen, COL11A1. The first of two cases reported here was the affected offspring of first cousins and sequence analysis excluded mutations in COL11A1. Consequently, whole-genome SNP genotyping was performed to identify blocks of homozygosity, identical-by-descent, wherein the disease locus would reside. COL11A1 was not within a region of homozygosity, further excluding it as the disease locus, but the gene encoding the proα2(XI) chain of type XI collagen, COL11A2, was located within a large region of homozygosity. Sequence analysis identified homozygosity for a splice donor mutation in intron 18. Exon trapping demonstrated that the mutation resulted in skipping of exon 18 and predicted deletion of 18 amino acids from the triple helical domain of the protein. In the second case, heterozygosity for a de novo 9 bp deletion in exon 40 of COL11A2 was identified, indicating that there are autosomal dominant forms of fibrochondrogenesis. These findings thus demonstrate that fibrochondrogenesis can result from either recessively or dominantly inherited mutations in COL11A2. © 2012 Wiley Periodicals, Inc.