Journal article
Fibrochondrogenesis Results from Mutations in the COL11A1 Type XI Collagen Gene
American journal of human genetics, Vol.87(5), pp.708-712
11/12/2010
DOI: 10.1016/j.ajhg.2010.10.009
PMCID: PMC2978944
PMID: 21035103
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.
Details
- Title: Subtitle
- Fibrochondrogenesis Results from Mutations in the COL11A1 Type XI Collagen Gene
- Creators
- Stuart W. Tompson - Cedars-Sinai Medical CenterCarlos A. Bacino - Baylor College of MedicineNicole P. Safina - Children's Hospital of The King's DaughtersMichael B. Bober - Alfred I. duPont Hospital for ChildrenVirginia K. Proud - Children's Hospital of The King's DaughtersTara Funari - Cedars-Sinai Medical CenterMichael F. Wangler - Baylor College of MedicineLisette Nevarez - Cedars-Sinai Medical CenterLeena Ala-Kokko - Tissue GeneWilliam R. Wilcox - University of California, Los AngelesDavid R. Eyre - University of WashingtonDeborah Krakow - University of California, Los AngelesDaniel H. Cohn - University of California, Los Angeles
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.87(5), pp.708-712
- Publisher
- Elsevier
- DOI
- 10.1016/j.ajhg.2010.10.009
- PMID
- 21035103
- PMCID
- PMC2978944
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Language
- English
- Date published
- 11/12/2010
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984353840802771
Metrics
6 Record Views