Myocilin mutations in a population-based sample of cases with open-angle glaucoma: the Rotterdam Study

被引:25
作者
Hulsman, CAA
de Jong, PTVM
Lettink, M
van Duijn, CM
Hofman, A
Bergen, AAB
机构
[1] Royal Netherlands Acad Arts & Sci, Netherlands Ophthalm Res Inst, NL-1105 BA Amsterdam, Netherlands
[2] Erasmus Univ, Sch Med, Dept Epidemiol & Biostat, Rotterdam, Netherlands
[3] Amsterdam Acad Med Ctr, Dept Ophthalmol, Amsterdam, Netherlands
关键词
D O I
10.1007/s00417-002-0455-1
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Purpose: To investigate the prevalence of myocilin (MYOC) mutations in a population-based sample of open-angle glaucoma (OAG) cases and to describe a family with both juvenile and adult onset OAG caused by a mutation in MYOC. Methods: MYOC was screened in cases derived from the Rotterdam Study in the Netherlands. Definite OAG was defined as a glaucomatous optic neuropathy together with a glaucomatous visual field defect. Upon the identification of the Asn480Lys mutation in one case, seven additional family members were studied. To test for a founder effect with earlier reported families with this mutation, the haplotypes of MYOC flanking markers D1S2851, D1S242, D1S218, and D I S 1165 were compared. Results: Seven sequence alterations in MYOC were found in 14 of 47 OAG cases; six of these were also found in controls. In one case, an Asn480Lys mutation was found. In relatives of the latter patient, the phenotype ranged from a glaucomatous optic neuropathy without visual field defect in a 70-year-old patient to severely affected optic discs and a remaining temporal remnant in a 34-year-old patient; those without the mutation had no signs of OAG. Haplotype analysis suggested a different origin of the mutation. Conclusions: The prevalence of MYOC mutations (2.2%) was similar to that found in hospital-based studies. Although mutations in MYOC are rare, relatives carrying this mutation run a high risk of developing the disease. Instead of submitting all members of a family with the Asn480Lys mutation to frequent follow-up, medical care can be restricted to those carrying the mutation.
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页码:468 / 474
页数:7
相关论文
共 42 条
  • [11] Karali A, 2000, INVEST OPHTH VIS SCI, V41, P729
  • [12] Regulation of human myocilin/TIGR gene transcription in trabecular meshwork cells and astrocytes: role of upstream stimulatory factor
    Kirstein, L
    Cvekl, A
    Chauhan, BK
    Tamm, ER
    [J]. GENES TO CELLS, 2000, 5 (08) : 661 - 676
  • [13] KLEIN BEK, 1992, OPHTHALMOLOGY, V99, P1499
  • [14] A novel myosin-like protein (Myocilin) expressed in the connecting cilium of the photoreceptor: Molecular cloning, tissue expression, and chromosomal mapping
    Kubota, R
    Noda, S
    Wang, YM
    Minoshima, S
    Asakawa, S
    Kudoh, J
    Mashima, Y
    Oguchi, Y
    Shimizu, N
    [J]. GENOMICS, 1997, 41 (03) : 360 - 369
  • [15] Lam DSC, 2000, INVEST OPHTH VIS SCI, V41, P1386
  • [16] THE EPIDEMIOLOGY OF OPEN-ANGLE GLAUCOMA - A REVIEW
    LESKE, MC
    [J]. AMERICAN JOURNAL OF EPIDEMIOLOGY, 1983, 118 (02) : 166 - 191
  • [17] THE BARBADOS EYE STUDY - PREVALENCE OF OPEN-ANGLE GLAUCOMA
    LESKE, MC
    CONNELL, AMS
    SCHACHAT, AP
    HYMAN, L
    [J]. ARCHIVES OF OPHTHALMOLOGY, 1994, 112 (06) : 821 - 829
  • [18] Lütjen-Drecoll E, 1998, INVEST OPHTH VIS SCI, V39, P517
  • [19] A GLC1A gene Gln368Stop mutation in a patient with normal-tension open-angle glaucoma
    Mardin, CY
    Velten, I
    Özbey, S
    Rautenstrauss, B
    Michels-Rautenstrauss, K
    [J]. JOURNAL OF GLAUCOMA, 1999, 8 (02) : 154 - 156
  • [20] Juvenile open angle glaucoma: fine mapping of the TIGR gene to 1q24.3-q25.2 and mutation analysis
    Michels-Rautenstrauss, KG
    Mardin, CY
    Budde, WM
    Liehr, T
    Polansky, J
    Nguyen, T
    Timmerman, V
    Van Broeckhoven, C
    Naumann, GOH
    Pfeiffer, RA
    Rautenstrauss, BW
    [J]. HUMAN GENETICS, 1998, 102 (01) : 103 - 106