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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1995 Mar;56(3):692–697.

Linkage of early-onset osteoarthritis and chondrocalcinosis to human chromosome 8q.

C T Baldwin 1, L A Farrer 1, R Adair 1, R Dharmavaram 1, S Jimenez 1, L Anderson 1
PMCID: PMC1801178  PMID: 7887424

Abstract

Calcium pyrophosphate-deposition disease (CPDD), also called "chondrocalcinosis" or "pseudogout," is a disorder characterized by the deposition of calcium-containing crystals in joint tissue, which leads to arthritis-like symptoms. The presence of these crystals in joint tissue is a common finding in the elderly, and, in this population, there is a poor correlation with joint pain. In contrast, early-onset CPDD has been described in several large families in which the disease progresses to severe degenerative osteoarthritis (OA). In these families, an autosomal dominant mode of inheritance is observed, with an age at onset between the 2d and 5th decades of life. In this report, we describe a large New England family with early-onset CPDD and severe degenerative OA. We found genetic linkage between the disease in this family and chromosome 8q, with a multipoint lod score of 4.06. These results suggest that a defective gene at this location causes the disease in this family.

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Selected References

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  1. Ahmad N. N., Ala-Kokko L., Knowlton R. G., Jimenez S. A., Weaver E. J., Maguire J. I., Tasman W., Prockop D. J. Stop codon in the procollagen II gene (COL2A1) in a family with the Stickler syndrome (arthro-ophthalmopathy). Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6624–6627. doi: 10.1073/pnas.88.15.6624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ala-Kokko L., Baldwin C. T., Moskowitz R. W., Prockop D. J. Single base mutation in the type II procollagen gene (COL2A1) as a cause of primary osteoarthritis associated with a mild chondrodysplasia. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6565–6568. doi: 10.1073/pnas.87.17.6565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Badley E. M., Rasooly I., Webster G. K. Relative importance of musculoskeletal disorders as a cause of chronic health problems, disability, and health care utilization: findings from the 1990 Ontario Health Survey. J Rheumatol. 1994 Mar;21(3):505–514. [PubMed] [Google Scholar]
  4. Balsa A., Martín-Mola E., Gonzalez T., Cruz A., Ojeda S., Gijón-Baños J. Familial articular chondrocalcinosis in Spain. Ann Rheum Dis. 1990 Jul;49(7):531–535. doi: 10.1136/ard.49.7.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bogaert R., Tiller G. E., Weis M. A., Gruber H. E., Rimoin D. L., Cohn D. H., Eyre D. R. An amino acid substitution (Gly853-->Glu) in the collagen alpha 1(II) chain produces hypochondrogenesis. J Biol Chem. 1992 Nov 5;267(31):22522–22526. [PubMed] [Google Scholar]
  6. Bowcock A. M., Farrer L. A., Cavalli-Sforza L. L., Hebert J. M., Kidd K. K., Frydman M., Bonne-Tamir B. Mapping the Wilson disease locus to a cluster of linked polymorphic markers on chromosome 13. Am J Hum Genet. 1987 Jul;41(1):27–35. [PMC free article] [PubMed] [Google Scholar]
  7. Braverman M. S. An algorithm to improve the computational efficiency of genetic linkage analysis. Comput Biomed Res. 1985 Feb;18(1):24–36. doi: 10.1016/0010-4809(85)90004-7. [DOI] [PubMed] [Google Scholar]
  8. Conneally P. M., Edwards J. H., Kidd K. K., Lalouel J. M., Morton N. E., Ott J., White R. Report of the Committee on Methods of Linkage Analysis and Reporting. Cytogenet Cell Genet. 1985;40(1-4):356–359. doi: 10.1159/000132186. [DOI] [PubMed] [Google Scholar]
  9. Doherty M., Hamilton E., Henderson J., Misra H., Dixey J. Familial chondrocalcinosis due to calcium pyrophosphate dihydrate crystal deposition in English families. Br J Rheumatol. 1991 Feb;30(1):10–15. doi: 10.1093/rheumatology/30.1.10. [DOI] [PubMed] [Google Scholar]
  10. Eshel G., Gulik A., Halperin N., Avrahami E., Schumacher H. R., McCarty D. J., Caspi D. Hereditary chondrocalcinosis in an Ashkenazi Jewish family. Ann Rheum Dis. 1990 Jul;49(7):528–530. doi: 10.1136/ard.49.7.528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fam A. G. Calcium pyrophosphate crystal deposition disease and other crystal deposition diseases. Curr Opin Rheumatol. 1992 Aug;4(4):574–582. [PubMed] [Google Scholar]
  12. Felson D. T., Anderson J. J., Naimark A., Kannel W., Meenan R. F. The prevalence of chondrocalcinosis in the elderly and its association with knee osteoarthritis: the Framingham Study. J Rheumatol. 1989 Sep;16(9):1241–1245. [PubMed] [Google Scholar]
  13. Gyapay G., Morissette J., Vignal A., Dib C., Fizames C., Millasseau P., Marc S., Bernardi G., Lathrop M., Weissenbach J. The 1993-94 Généthon human genetic linkage map. Nat Genet. 1994 Jun;7(2 Spec No):246–339. doi: 10.1038/ng0694supp-246. [DOI] [PubMed] [Google Scholar]
  14. Hamza M., Meddeb N., Bardin T. Hereditary chondrocalcinosis in a Tunisian family. Clin Exp Rheumatol. 1992 Jan-Feb;10(1):43–49. [PubMed] [Google Scholar]
  15. Ledingham J., Dawson S., Preston B., Milligan G., Doherty M. Radiographic patterns and associations of osteoarthritis of the hip. Ann Rheum Dis. 1992 Oct;51(10):1111–1116. doi: 10.1136/ard.51.10.1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lee B., Vissing H., Ramirez F., Rogers D., Rimoin D. Identification of the molecular defect in a family with spondyloepiphyseal dysplasia. Science. 1989 May 26;244(4907):978–980. doi: 10.1126/science.2543071. [DOI] [PubMed] [Google Scholar]
  17. Murray J. C., Buetow K. H., Weber J. L., Ludwigsen S., Scherpbier-Heddema T., Manion F., Quillen J., Sheffield V. C., Sunden S., Duyk G. M. A comprehensive human linkage map with centimorgan density. Cooperative Human Linkage Center (CHLC). Science. 1994 Sep 30;265(5181):2049–2054. doi: 10.1126/science.8091227. [DOI] [PubMed] [Google Scholar]
  18. Naccache P. H., Bourgoin S., Plante E., Roberge C. J., de Medicis R., Lussier A., Poubelle P. E. Crystal-induced neutrophil activation. II. Evidence for the activation of a phosphatidylcholine-specific phospholipase D. Arthritis Rheum. 1993 Jan;36(1):117–125. doi: 10.1002/art.1780360119. [DOI] [PubMed] [Google Scholar]
  19. Oehlmann R., Summerville G. P., Yeh G., Weaver E. J., Jimenez S. A., Knowlton R. G. Genetic linkage mapping of multiple epiphyseal dysplasia to the pericentromeric region of chromosome 19. Am J Hum Genet. 1994 Jan;54(1):3–10. [PMC free article] [PubMed] [Google Scholar]
  20. Pattrick M., Hamilton E., Wilson R., Austin S., Doherty M. Association of radiographic changes of osteoarthritis, symptoms, and synovial fluid particles in 300 knees. Ann Rheum Dis. 1993 Feb;52(2):97–103. doi: 10.1136/ard.52.2.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pun Y. L., Moskowitz R. W., Lie S., Sundstrom W. R., Block S. R., McEwen C., Williams H. J., Bleasel J. F., Holderbaum D., Haqqi T. M. Clinical correlations of osteoarthritis associated with a single-base mutation (arginine519 to cysteine) in type II procollagen gene. A newly defined pathogenesis. Arthritis Rheum. 1994 Feb;37(2):264–269. doi: 10.1002/art.1780370216. [DOI] [PubMed] [Google Scholar]
  22. Richardson B. C., Chafetz N. I., Ferrell L. D., Zulman J. I., Genant H. K. Hereditary chondrocalcinosis in a Mexican-American family. Arthritis Rheum. 1983 Nov;26(11):1387–1396. doi: 10.1002/art.1780261112. [DOI] [PubMed] [Google Scholar]
  23. Ryan L. M. Calcium pyrophosphate dihydrate crystal deposition and other crystal deposition diseases. Curr Opin Rheumatol. 1993 Jul;5(4):517–521. doi: 10.1097/00002281-199305040-00018. [DOI] [PubMed] [Google Scholar]
  24. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  25. Sanmartí R., Pañella D., Brancós M. A., Canela J., Collado A., Brugués J. Prevalence of articular chondrocalcinosis in elderly subjects in a rural area of Catalonia. Ann Rheum Dis. 1993 Jun;52(6):418–422. doi: 10.1136/ard.52.6.418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tiller G. E., Rimoin D. L., Murray L. W., Cohn D. H. Tandem duplication within a type II collagen gene (COL2A1) exon in an individual with spondyloepiphyseal dysplasia. Proc Natl Acad Sci U S A. 1990 May;87(10):3889–3893. doi: 10.1073/pnas.87.10.3889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Vissing H., D'Alessio M., Lee B., Ramirez F., Godfrey M., Hollister D. W. Glycine to serine substitution in the triple helical domain of pro-alpha 1 (II) collagen results in a lethal perinatal form of short-limbed dwarfism. J Biol Chem. 1989 Nov 5;264(31):18265–18267. [PubMed] [Google Scholar]
  28. Warman M. L., Abbott M., Apte S. S., Hefferon T., McIntosh I., Cohn D. H., Hecht J. T., Olsen B. R., Francomano C. A. A type X collagen mutation causes Schmid metaphyseal chondrodysplasia. Nat Genet. 1993 Sep;5(1):79–82. doi: 10.1038/ng0993-79. [DOI] [PubMed] [Google Scholar]
  29. Williams C. J., Considine E. L., Knowlton R. G., Reginato A., Neumann G., Harrison D., Buxton P., Jimenez S., Prockop D. J. Spondyloepiphyseal dysplasia and precocious osteoarthritis in a family with an Arg75-->Cys mutation in the procollagen type II gene (COL2A1). Hum Genet. 1993 Nov;92(5):499–505. doi: 10.1007/BF00216458. [DOI] [PubMed] [Google Scholar]

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