Autosomal dominant and recessive osteochondrodysplasias associated with the COL11A2 locus

Abstract

Identifying mutations that cause specific osteochondrodysplasias will provide novel insights into the function of genes that are essential for skeletal morphogenesis. We report here that an autosomal dominant form of Stickler syndrome, characterized by mild spondyloepiphyseal dysplasia, osteoarthritis, and sensorineural hearing loss, but no eye involvement, is caused by a splice donor site mutation resulting in "in-frame" exon skipping within the COL11A2 gene, encoding the alpha 2(XI) chain of the quantitatively minor fibrillar collagen XI. We also show that an autosomal recessive disorder with similar, but more severe, characteristics is linked to the COL11A2 locus and is caused by a glycine to arginine substitution in alpha 2(XI) collagen. The results suggest that mutations in collagen XI genes are associated with a spectrum of abnormalities in human skeletal development and support the conclusion of others, based on studies of murine chondrodysplasia, that collagen XI is essential for skeletal morphogenesis.

Genetic causes of nonsyndromic hearing loss in Iran in comparison with other populations

“…COL11A2 mutations can generate both autosomal recessive and progressive autosomal dominant HL (DFNB53 and DFNA13). [91][92][93] …”

Evaluation and management of pediatric rhegmatogenous retinal detachment

“…29,30 Type III Stickler syndrome and Weissenbacher-Zweymuller syndrome are caused by dominant mutations in COL11A2, but are not associated with an ocular phenotype. 31,32 A rare autosomal recessive form Stickler syndrome that does have ocular involvement has also recently been described and is associated with mutations in the COL9A1 gene. 33 …”

HLA-DPB1-COL11A2 and three additional xMHC loci are independently associated with RA in a UK cohort

“…This pattern was similar to that found by Lee et al 15 Polymorphisms in COL11A2 have been implicated in susceptibility to skeletal and cartilage disorders, and hearing loss. [27][28][29][30][31][32] HLA-DPB1 is an attractive candidate gene for RA within this region, as it has an important role in the immune system by presenting peptides to CD4 þ T cells. Furthermore, the other two genes encoding classical HLA class II molecules, HLA-DRB1 and HLA-DQA1, are established RA risk genes.…”