Disease relevance of COL11A2

• We therefore analyzed a cohort of 24 patients with nonsyndromic Robin sequence, 17 with nonsyndromic cleft palate and 21 with nonsyndromic micrognathia for mutations in COL11A2 [1].
• In addition, an IVS6-4 a>t polymorphism in COL11A2 has been found in connection with stenosis caused by ossification of the posterior longitudinal ligament in the Japanese population [2].
• We found two families (one American and one Dutch) with autosomal dominant, non-syndromic hearing loss to have mutations in COL11A2 that are predicted to affect the triple-helix domain of the collagen protein [3].
• Autosomal dominant and recessive osteochondrodysplasias associated with the COL11A2 locus [4].
• COL11A2 collagen gene transcription is differentially regulated by EWS/ERG sarcoma fusion protein and wild-type ERG [5].

Psychiatry related information on COL11A2

• Members of a Dutch DFNA13/COL11A2 family were evaluated with pure tone audiometry, stapedial reflexes, otoacoustic emissions, loudness scaling, difference limen for frequency, gap detection, and speech perception in quiet and noise [6].

High impact information on COL11A2

• Mutations in COL11A2 cause non-syndromic hearing loss (DFNA13) [3].
• We report that mutation of COL11A2 causes deafness previously mapped to the DFNA13 locus on chromosome 6p [3].
• 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 [4].
• It has an autosomal dominant inheritance pattern and is caused by mutations in COL2A1, COL11A1, and COL11A2 [7].
• We conclude that the OSMED phenotype is highly homogenous and results from homozygosity or compound heterozygosity for COL11A2 mutations, most of which are predicted to cause complete absence of alpha2(XI) chains [8].

Biological context of COL11A2

• COL11A2 is 30.5 kb with a minimum of 62 exons, differing from other reported fibrillar collagen genes because the amino propeptide is encoded by 14 not 5 to 8 exons [9].
• The promoter region of COL11A2 lacks a TATA box but is GC-rich with two potential SP1 binding sites [9].
• We provide data that complete information for the coding sequence of human alpha 2(XI) procollagen, with details of the promoter region and intron-exon organization at the 5' and 3' ends of the gene (COL11A2), including the transcription start and polyadenylation sites [9].
• Oto- spondylo-megaepiphyseal dysplasia (OSMED): clinical description of three patients homozygous for a missense mutation in the COL11A2 gene [10].
• The human COL11A2 gene was analyzed from two overlapping cosmid clones that were previously isolated in the course of searching the human major histocompatibility region (Janatipour, M., Naumov, Y., Ando, A., Sugimura, K., Okamoto, N., Tsuji, K., Abe, K., and Inoko, H. (1992) Immunogenetics 35, 272-278) [11].

Anatomical context of COL11A2

• We found that both the EWS/ERG and COL11A2 genes are expressed in the Ewing's sarcoma cell line, CADO-ES1 [5].
• Using a cloned fragment of the human alpha 2(XI) collagen gene (COL11A2) as a molecular probe for in situ hybridization and somatic cell hybrid mapping, we have localized the gene to the short arm of chromosome 6, region 21 [12].
• MATERIALS AND METHODS: We cultured Saos-2 cells, a human osteosarcoma-derived line of osteoblasts, and analyzed them for alpha2(XI) protein and COL11A2 regulatory mechanisms [13].
• Another Sp1 family member, Sp7 (Osterix), was expressed in Saos-2 cells, but not in chondrocytes, and was shown by chromatin immunoprecipitation to occupy the COL11A2 promoter [13].
• As a first step toward a functional analysis of type XI collagen, a member of this class of poorly understand "minor" collagen proteins which is expressed primarily in hyaline cartilage, we have used human probes for the gene encoding the protein's alpha 2-subunit (COL11A2) to isolate and map homologous murine DNA sequences [14].

Associations of COL11A2 with chemical compounds

• Considering these phenotypic similarities and the close association between the COL11A1 and COL11A2 gene products, we propose that Marshall syndrome may be caused by a mutation in COL11A1 [10].
• Heterozygous glycine substitution in the COL11A2 gene in the original patient with the Weissenbacher-Zweymüller syndrome demonstrates its identity with heterozygous OSMED (nonocular Stickler syndrome) [15].
• Overexpressing Sp7 increased COL11A2 promoter activity and endogenous gene expression, an effect also blocked by mithramycin A [13].
• Depsipeptide also up-regulated the expressions of aggrecan and the alpha2 chain of type XI collagen (COL11A2) mRNA in a dose-dependent manner [16].
• Nucleotide sequencing of the PCR product demonstrated that PARP is a fragment of the NH2-terminal non-collagenous (NC3) domain of the collagen alpha 2(XI) chain [17].

Other interactions of COL11A2

• Linkage to candidate genes COL9A1, COL9A2, and COL11A2 was tested and excluded for both genetic models in this family [18].
• We detected two disease-associated mutations in patients with Robin sequence, an Arg to stop codon mutation in COL11A2 and a splicing mutation in COL11A1 [1].
• The COL11A2, COL2A1 and IL-1beta(C(3954)-T) polymorphisms were also analysed [19].
• The retinoid X receptor beta (RXR beta) gene is located 1.1 kb upstream of COL11A2 [9].
• Ossification of the posterior longitudinal ligament (OPLL) of the spine is the leading cause of myelopathy in Japan. In earlier studies, we provided genetic linkage and allelic association evidence of distinct differences in the human collagen alpha2(XI) gene (COL11A2) that might constitute inherited predisposition to OPLL [20].

Analytical, diagnostic and therapeutic context of COL11A2

• The human alpha 2(XI) collagen (COL11A2) chain. Molecular cloning of cDNA and genomic DNA reveals characteristics of a fibrillar collagen with differences in genomic organization [21].
• COL11A2 was highly expressed on days 0 and 5, but the expression levels were rapidly decreased on day 9 by Northern blot analysis [22].
• From the gene mapping of this abnormality, the abnormal N-propeptide of the COL11A2 gene was found to be responsible [23].
• Subsequently, a reverse transcription-polymerase chain reaction (RT-PCR) was performed with poly(A)-rich RNA from human cartilage using a sense oligonucleotide derived from PARP and an anti-sense oligonucleotide derived from the known sequence of the human collagen alpha 2(XI) chain [2] [17].
• Moreover, the expression of cytochrome C, caspases 3 and 8 and PARP genes was increased after treatment and the gradual reduction of Bcl-XL protein was observed, which indicate that the apoptotic signals were induced after treatment by troglitazone [24].

References