Fibrochondrogenesis results from mutations in the COL11A1 type XI collagen gene.
Publication/Presentation Date
11-12-2010
Abstract
Fibrochondrogenesis is a severe, autosomal-recessive, short-limbed skeletal dysplasia. In a single case of fibrochondrogenesis, whole-genome SNP genotyping identified unknown ancestral consanguinity by detecting three autozygous regions. Because of the predominantly skeletal nature of the phenotype, the 389 genes localized to the autozygous intervals were prioritized for mutation analysis by correlation of their expression with known cartilage-selective genes via the UCLA Gene Expression Tool, UGET. The gene encoding the α1 chain of type XI collagen (COL11A1) was the only cartilage-selective gene among the three candidate intervals. Sequence analysis of COL11A1 in two genetically independent fibrochondrogenesis cases demonstrated that each was a compound heterozygote for a loss-of-function mutation on one allele and a mutation predicting substitution for a conserved triple-helical glycine residue on the other. The parents who were carriers of missense mutations had myopia. Early-onset hearing loss was noted in both parents who carried a loss-of-function allele, suggesting COL11A1 as a locus for mild, dominantly inherited hearing loss. These findings identify COL11A1 as a locus for fibrochondrogenesis and indicate that there might be phenotypic manifestations among carriers.
Volume
87
Issue
5
First Page
708
Last Page
712
ISSN
1537-6605
Published In/Presented At
Tompson, S. W., Bacino, C. A., Safina, N. P., Bober, M. B., Proud, V. K., Funari, T., Wangler, M. F., Nevarez, L., Ala-Kokko, L., Wilcox, W. R., Eyre, D. R., Krakow, D., & Cohn, D. H. (2010). Fibrochondrogenesis results from mutations in the COL11A1 type XI collagen gene. American journal of human genetics, 87(5), 708–712. https://doi.org/10.1016/j.ajhg.2010.10.009
Disciplines
Medicine and Health Sciences
PubMedID
21035103
Department(s)
Department of Pathology and Laboratory Medicine
Document Type
Article