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NM_001844.5(COL2A1):c.2155C>T (p.Arg719Cys) AND Osteoarthritis with mild chondrodysplasia

Significance: Pathogenic
ClinVar: RCV000018896

Variant: NM_001844.5(COL2A1):c.2155C>T (p.Arg719Cys)

Type: Variant
Allele: NM_001844.5(COL2A1):c.2155C>T (p.Arg719Cys) 32392
Gene:
Type: single nucleotide variant
Location: Chr12: 47982886 - assembly GRCh38
Chr12: 48376669 - assembly GRCh37
References: dbSNP: 121912865
OMIM: 120140.0003
UniProtKB: P02458#VAR_001748

Condition

Disease: Osteoarthritis with mild chondrodysplasia

Citations

    In the kindred described by Knowlton et al. (1990) with osteoarthritis associated with mild chondrodysplasia (OSCDP; 604864), Ala-Kokko et al. (1990) found a heterozygous change from arginine to cysteine at position 519 of the alpha-1(II) chain. In an affected family member who underwent hip surgery, Eyre et al. (1991) demonstrated that approximately one-fourth of the alpha-1(II) chains present in the polymeric extracellular collagen of the patient's cartilage contained the arg519-to-cys substitution. The protein exhibited other abnormal properties including disulfide-bonded alpha-1(II) dimers and signs of posttranslational overmodification.
PMID:, PMID:1975693, PMID:1985108
    Williams et al. (1995) found the arg519-to-cys mutation in a fourth family with early-onset osteoarthritis and late-onset spondyloepiphyseal dysplasia.
PMID:7757086
    Holderbaum et al. (1993) referred to 2 additional families with precocious-onset osteoarthritis and mild chondrodysplasia caused by the arg519-to-cys mutation. They reported studies suggesting that the mutation arose independently in at least 2 of the 3 known affected families.
PMID:8507190
    Bleasel et al. (1998) reported that the arg519-to-cys mutation in COL2A1 had been identified in 5 families with mild spondyloepiphyseal dysplasia and precocious osteoarthritis. Haplotype analysis identified 3 distinct mutation-bearing haplotypes, with 3 families sharing a common haplotype. For the 3 distinct haplotypes to have derived from a single founder, 3 independent recombination events were required. Thus, the arg519 codon appears to represent a possible site of recurrent mutations in COL2A1, an uncommon phenomenon in collagen genes.
PMID:9711874