PROTECTIVE PROTEIN GENE-MUTATIONS IN GALACTOSIALIDOSIS

被引:57
作者
SHIMMOTO, M
FUKUHARA, Y
ITOH, K
OSHIMA, A
SAKURABA, H
SUZUKI, Y
机构
[1] Department of Clinical Genetics, Tokyo Metropol. Inst. of Med. Sci., Tokyo
[2] Department of Clinical Genetics, Tokyo Metropol. Inst. of Med. Sci., Bunkyo-ku, Tokyo 113
关键词
CARBOXYPEPTIDASE; BETA-GALACTOSIDASE; NEURAMINIDASE; PHENOTYPE; GENOTYPE;
D O I
10.1172/JCI116472
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Four different protective protein cDNA mutations, 146A --> G (Q49R), 193T --> C (W65R), 268-269TC --> CT (S90L), and 1184A --> G (Y395C), were identified in six Japanese galactosialidosis patients with various phenotypic manifestations, and another mutation, 746T --> A (Y249N), in a patient of French-German origin with an atypical clinical course. Y395C was a common mutation in four Japanese patients in infancy and childhood; two juvenile patients were compound heterozygotes of Y395C and another common mutation, SpDEx7, and the other two infants were compound heterozygotes of Y395C and mutant alleles other than SpDEx7. We confirmed these mutations in genomic DNA by direct-sequence analysis or restriction-site analysis. The mutant cDNA clones, transiently expressed in a transformed galactosialidosis cell line, did not restore the secondarily deficient beta-galactosidase or alpha-neuraminidase activity except for the Y249N mutation that expressed some carboxypeptidase activity and restored the two lysosomal enzyme activities. Pulse-chase analysis detected a small amount of the mature form, as well as the precursor, in the cells transfected with the Y249N cDNA. Only precursor proteins were detected, mature proteins not appearing for the other mutant cDNAs.
引用
收藏
页码:2393 / 2398
页数:6
相关论文
共 25 条
  • [1] BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
  • [2] MOLECULAR DEFECT IN COMBINED BETA-GALACTOSIDASE AND NEURAMINIDASE DEFICIENCY IN MAN
    DAZZO, A
    HOOGEVEEN, A
    REUSER, AJJ
    ROBINSON, D
    GALJAARD, H
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1982, 79 (15): : 4535 - 4539
  • [3] Fukuhara Yukiko, 1992, Brain Dysfunction, V5, P319
  • [4] EXPRESSION OF CDNA-ENCODING THE HUMAN PROTECTIVE PROTEIN ASSOCIATED WITH LYSOSOMAL BETA-GALACTOSIDASE AND NEURAMINIDASE - HOMOLOGY TO YEAST PROTEASES
    GALJART, NJ
    GILLEMANS, N
    HARRIS, A
    VANDERHORST, GTJ
    VERHEIJEN, FW
    GALJAARD, H
    DAZZO, A
    [J]. CELL, 1988, 54 (06) : 755 - 764
  • [5] GALJART NJ, 1990, J BIOL CHEM, V265, P4678
  • [6] HOOGEVEEN AT, 1983, J BIOL CHEM, V258, P2143
  • [7] ACID CARBOXYPEPTIDASE DEFICIENCY IN GALACTOSIALIDOSIS
    ITOH, K
    TAKIYAMA, N
    NAGAO, Y
    OSHIMA, A
    SAKURABA, H
    POTIER, M
    SUZUKI, Y
    [J]. JAPANESE JOURNAL OF HUMAN GENETICS, 1991, 36 (02): : 171 - 177
  • [8] JACKMAN HL, 1990, J BIOL CHEM, V265, P11265
  • [9] GALACTOSIALIDOSIS - SIMULTANEOUS DEFICIENCY OF ESTERASE, CARBOXY-TERMINAL DEAMIDASE AND ACID CARBOXYPEPTIDASE ACTIVITIES
    KASE, R
    ITOH, K
    TAKIYAMA, N
    OSHIMA, A
    SAKURABA, H
    SUZUKI, Y
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 172 (03) : 1175 - 1179
  • [10] MIYAZAKI J, 1989, GENE, V79, P269