Werner syndrome: Characterization of mutations in the WRN gene in an affected family

被引:12
作者
Meisslitzer, C
Ruppitsch, W
Weirich-Schwaiger, H
Weirich, HG
Jabkowsky, J
Klein, G
Schweiger, M
Hirsch-Kauffmann, M
机构
[1] Free Univ Berlin, Inst Biochem, D-14195 Berlin, Germany
[2] Allgemeines Offentliches Krankenhaus Elisabethine, Dermatol Abt, Linz, Austria
[3] Inst Med Biol & Human Genet, Innsbruck, Austria
关键词
Werner syndrome; splice mutation; WRN gene; WRN protein; DNA repair;
D O I
10.1159/000484793
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Affected and unaffected members of a Caucasian family with Werner syndrome were analyzed for mutations in the recently described Werner syndrome (WRN) gene and for their relevance to phenotypic expression of chromosomal instability and x-ray hypersensitivity. Two distinct molecular alterations were documented in the family, Analysis of the genomic DNA revealed a single-base exchange from A to T at an intron-exon boundary in the otherwise strongly conserved 5' donor splice site. Consequently, exon 30 is spliced together with the intron, The ensuing structure could be confirmed by the presence and calculated size of the resulting RNA fragments. The patients, all compound heterozygotes, had a l-bp deletion in the first third of the coding sequence in the other allele. The genotypes of the family members for these mutations were determined and consequences for the cellular phenotype of the otherwise unaffected heterozygotes are documented.
引用
收藏
页码:364 / 370
页数:7
相关论文
共 21 条
[1]   PRODUCTION OF MICRONUCLEI FROM CHROMOSOME-ABERRATIONS IN IRRADIATED CULTURES OF HUMAN LYMPHOCYTES [J].
COUNTRYMAN, PI ;
HEDDLE, JA .
MUTATION RESEARCH, 1976, 41 (2-3) :321-331
[2]   WERNERS SYNDROME - A REVIEW OF ITS SYMPTOMATOLOGY NATURAL HISTORY PATHOLOGIC FEATURES GENETICS AND RELATIONSHIP TO NATURAL AGING PROCESS [J].
EPSTEIN, CJ ;
MARTIN, GM ;
SCHULTZ, AL ;
MOTULSKY, AG .
MEDICINE, 1966, 45 (03) :177-+
[3]   RETARDED RATE OF DNA-REPLICATION AND NORMAL LEVEL OF DNA-REPAIR IN WERNERS SYNDROME FIBROBLASTS IN CULTURE [J].
FUJIWARA, Y ;
HIGASHIKAWA, T ;
TATSUMI, M .
JOURNAL OF CELLULAR PHYSIOLOGY, 1977, 92 (03) :365-374
[4]   Analysis of helicase gene mutations in Japanese Werner's syndrome patients [J].
Goto, M ;
Imamura, O ;
Kuromitsu, J ;
Matsumoto, T ;
Yamabe, Y ;
Tokutake, Y ;
Suzuki, N ;
Mason, B ;
Drayna, D ;
Sugawara, M ;
Sugimoto, M ;
Furuichi, Y .
HUMAN GENETICS, 1997, 99 (02) :191-193
[5]  
GOTO M, 1985, ADV EXP MED BIOL, V190, P245
[6]  
GOTO M, 1981, CLIN GENET, V19, P8
[7]   NORMAL LEVEL OF UNSCHEDULED DNA-SYNTHESIS IN WERNERS SYNDROME FIBROBLASTS IN CULTURE [J].
HIGASHIKAWA, T ;
FUJIWARA, Y .
EXPERIMENTAL CELL RESEARCH, 1978, 113 (02) :438-442
[8]  
MARTIN GM, 1970, LAB INVEST, V23, P86
[9]   Homozygous and compound heterozygous mutations at the Werner syndrome locus [J].
Oshima, J ;
Yu, CE ;
Piussan, C ;
Klein, G ;
Jabkowski, J ;
Balci, S ;
Miki, T ;
Nakura, J ;
Ogihara, T ;
Ells, J ;
Smith, MDC ;
Melaragno, MI ;
Fraccaro, M ;
Scappaticci, S ;
Matthews, J ;
Ouais, S ;
Jarzebowicz, A ;
Schellenberg, GD ;
Martin, GM .
HUMAN MOLECULAR GENETICS, 1996, 5 (12) :1909-1913
[10]   IMPAIRED S-PHASE TRANSIT OF WERNER SYNDROME CELLS EXPRESSED IN LYMPHOBLASTOID CELL-LINES [J].
POOT, M ;
HOEHN, H ;
RUNGER, TM ;
MARTIN, GM .
EXPERIMENTAL CELL RESEARCH, 1992, 202 (02) :267-273