NOVEL ALLELES, HEMIZYGOSITY AND DELETIONS AT AN ALU-REPEAT WITHIN THE NEUROFIBROMATOSIS TYPE-1 (NF1) GENE

被引:43
作者
LAZARO, C
GAONA, A
RAVELLA, A
VOLPINI, V
CASALS, T
FUENTES, JJ
ESTIVILL, X
机构
[1] IRO HOSP DURAN & REYNALS, CANC RES INST, DEPT MOLEC GENET, E-08907 BARCELONA, SPAIN
[2] HOSP CREU ROJA DE BARCELONA, SERV DERMATOL, E-08025 BARCELONA, SPAIN
[3] HOSP CLIN BARCELONA, SERV GENET, E-08036 BARCELONA, SPAIN
关键词
D O I
10.1093/hmg/2.6.725
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
Neurofibromatosis type 1 (NF1) (von Recklinghausen) is a common autosomal dominant disorder, characterised by the presence of peripheral neurofibromas, cafe-au-lait spots and Lisch nodules of the iris. Due to the high mutation rate at the NF1 locus, most patients are expected to have different mutations, limiting molecular analysis and genetic counseling to the identification of the mutation in each patient or family, or to the use of DNA polymorphisms. We have analysed an Alu-repeat polymorphic sequence (AAAT), located in intron 27 of the NF1 gene, in 70 NF1 and 40 CEPH families and we have detected several genetic and molecular abnormalities. In two families the NF1 individuals were hemizygous at the AAAT-repeat and/or at the CA-repeat of intron 27 of NF1, due to interstitial deletions, which include intron 27 to exon 37 of the NF1 gene. A 71-bp deletion at the Alu sequence was detected in non-NF1 chromosomes of members of three NF1 families. New alleles at the AAAT-repeat were found in one NF1 family and in three CEPH families giving a mutation rate for this AAAT-repeat of 0.36% per allele, which is one of the highest detected for a microsatellite locus.
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页码:725 / 730
页数:6
相关论文
共 43 条
  • [1] AINSWORTH PJ, 1991, AM J HUM GENET, V49, P1098
  • [2] A HIGHLY POLYMORPHIC CDNA PROBE IN THE NF1 GENE
    ANDERSEN, LB
    WALLACE, MR
    MARCHUK, DA
    TAVAKKOL, R
    MITCHELL, A
    SAULINO, AM
    COLLINS, FS
    [J]. NUCLEIC ACIDS RESEARCH, 1991, 19 (13) : 3754 - 3754
  • [3] A POLYMORPHIC CDNA PROBE ON CHROMOSOME-17Q11.2 LOCATED WITHIN THE NF1 GENE [D17S376]
    ANDERSEN, LB
    WALLACE, MR
    MARCHUK, DA
    CAWTHON, RM
    ODEH, HM
    LETCHER, R
    WHITE, RL
    COLLINS, FS
    [J]. NUCLEIC ACIDS RESEARCH, 1991, 19 (01) : 197 - 197
  • [4] Growth rate characteristics of acoustic neuromas associated with neurofibromatosis type 2
    Abaza, MM
    Makariou, E
    Armstrong, M
    Lalwani, AK
    [J]. LARYNGOSCOPE, 1996, 106 (06) : 694 - 699
  • [5] GENE FOR VON RECKLINGHAUSEN NEUROFIBROMATOSIS IS IN THE PERICENTROMERIC REGION OF CHROMOSOME-17
    BARKER, D
    WRIGHT, E
    NGUYEN, K
    CANNON, L
    FAIN, P
    GOLDGAR, D
    BISHOP, DT
    CAREY, J
    BATY, B
    KIVLIN, J
    WILLARD, H
    WAYE, JS
    GREIG, G
    LEINWAND, L
    NAKAMURA, Y
    OCONNELL, P
    LEPPERT, M
    LALOUEL, JM
    WHITE, R
    SKOLNICK, M
    [J]. SCIENCE, 1987, 236 (4805) : 1100 - 1102
  • [6] MSPI RFLP AT CRYB1 LOCUS (17Q11.2-]17Q12)
    BARKER, DF
    FAIN, PR
    WRIGHT, EC
    NGUYEN, K
    TSUI, LC
    [J]. NUCLEIC ACIDS RESEARCH, 1989, 17 (02) : 827 - 827
  • [7] A HUMAN-SPECIFIC SUBFAMILY OF ALU-SEQUENCES
    BATZER, MA
    DEININGER, PL
    [J]. GENOMICS, 1991, 9 (03) : 481 - 487
  • [8] A MAJOR SEGMENT OF THE NEUROFIBROMATOSIS TYPE-1 GENE - CDNA SEQUENCE, GENOMIC STRUCTURE, AND POINT MUTATIONS
    CAWTHON, RM
    WEISS, R
    XU, GF
    VISKOCHIL, D
    CULVER, M
    STEVENS, J
    ROBERTSON, M
    DUNN, D
    GESTELAND, R
    OCONNELL, P
    WHITE, R
    [J]. CELL, 1990, 62 (01) : 193 - 201
  • [9] CLEMENS PR, 1991, AM J HUM GENET, V49, P951
  • [10] ESTIVILL X, 1991, HUM GENET, V88, P185