Autosomal Dominant and Recessive Osteochondrodysplasias Associated with the COL11A2 Locus
Overview
Authors
Affiliations
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.
Lee N, Uhler K, Yoon P, Santos-Cortez R Biomedicines. 2024; 12(7).
PMID: 39062005 PMC: 11274279. DOI: 10.3390/biomedicines12071427.
Orthobiologics in knee osteoarthritis, dream or reality?.
Budhiparama N, Putramega D, Lumban-Gaol I Arch Orthop Trauma Surg. 2024; 144(9):3937-3946.
PMID: 38630251 PMC: 11564396. DOI: 10.1007/s00402-024-05310-9.
Age-dependent genetic regulation of osteoarthritis: independent effects of immune system genes.
Kenny J, Mullin B, Tomlinson W, Robertson B, Yuan J, Chen W Arthritis Res Ther. 2023; 25(1):232.
PMID: 38041181 PMC: 10691153. DOI: 10.1186/s13075-023-03216-2.
COL11A2 as a candidate gene for vertebral malformations and congenital scoliosis.
Rebello D, Wohler E, Erfani V, Li G, Aguilera A, Santiago-Cornier A Hum Mol Genet. 2023; 32(19):2913-2928.
PMID: 37462524 PMC: 10508038. DOI: 10.1093/hmg/ddad117.
Diaz Perez K, Chung S, Head S, Epstein M, Hecht J, Wehby G Am J Med Genet A. 2023; 191(10):2558-2570.
PMID: 37350193 PMC: 10528230. DOI: 10.1002/ajmg.a.63336.