LINKAGE ANALYSIS WITH CHROMOSOME-15Q11-13 MARKERS SHOWS GENOMIC IMPRINTING IN FAMILIAL ANGELMAN SYNDROME

被引:53
作者
MEIJERSHEIJBOER, EJ
SANDKUIJL, LA
BRUNNER, HG
SMEETS, HJM
HOOGEBOOM, AJM
DEELEN, WH
VANHEMEL, JO
NELEN, MR
SMEETS, DFCM
NIERMEIJER, MF
HALLEY, DJJ
机构
[1] ERASMUS UNIV,3000 DR ROTTERDAM,NETHERLANDS
[2] UNIV HOSP NIJMEGEN,DEPT HUMAN GENET,NIJMEGEN,NETHERLANDS
关键词
D O I
10.1136/jmg.29.12.853
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Angelman syndrome (AS) and Prader-Willi syndrome (PWS) have become the classical examples of genomic imprinting in man, as completely different phenotypes are generated by the absence of maternal (AS) or paternal (PWS) contributions to the q11-13 region of chromosome 15 as a result of deletion or uniparental disomy. Apparently, most patients are sporadic cases. The genetic mechanism underlying familial AS has remained enigmatic for a long time. Recently, evidence has been emerging suggesting autosomal dominant inheritance of a detectable or undetectable defect in a gene or genes at 15q11-13, subject to genomic imprinting. The present report describes an unusually large pedigree with segregation of AS through maternal inheritance and apparent asymptomatic transmission through several male ancestors. Deletion and paternal disomy at 15q11-13 were excluded. However, the genetic defect is still located in this region, as we obtained a maximum lod score of 5.40 for linkage to the GABA receptor locus GABRB3 and the anonymous DNA marker D15S10, which have been mapped within or adjacent to the AS critical region at 15q11-13. The size of the pedigree allowed calculation of an odds ratio in favour of genomic imprinting of 9.25 x 10(5). This family illustrates the necessity of extensive pedigree analysis when considering recurrence risks for relatives of AS patients, those without detectable deletion or disomy in particular.
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页码:853 / 857
页数:5
相关论文
共 26 条
  • [21] GENETIC IMPRINTING SUGGESTED BY MATERNAL HETERODISOMY IN NONDELETION PRADER-WILLI SYNDROME
    NICHOLLS, RD
    KNOLL, JHM
    BUTLER, MG
    KARAM, S
    LALANDE, M
    [J]. NATURE, 1989, 342 (6247) : 281 - 285
  • [22] PRADER A, 1956, SCHWEIZERISCHE MEDIZ, V86, P1260, DOI DOI 10.1007/978-3-642-47669-3_24
  • [23] FAMILIAL ANGELMAN SYNDROME CAUSED BY IMPRINTED SUBMICROSCOPIC DELETION ENCOMPASSING GABA-A RECEPTOR BETA-3-SUBUNIT GENE
    SAITOH, S
    KUBOTA, T
    OHTA, T
    JINNO, Y
    NIIKAWA, N
    SUGIMOTO, T
    WAGSTAFF, J
    LALANDE, M
    [J]. LANCET, 1992, 339 (8789) : 366 - 367
  • [24] PRADER-WILLI SYNDROME AND ANGELMAN SYNDROME IN COUSINS FROM A FAMILY WITH A TRANSLOCATION BETWEEN CHROMOSOME-6 AND CHROMOSOME-15
    SMEETS, DFCM
    HAMEL, BCJ
    NELEN, MR
    SMEETS, HJM
    BOLLEN, JHM
    SMITS, APT
    ROPERS, HH
    VANOOST, BA
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1992, 326 (12) : 807 - 811
  • [25] MATERNAL BUT NOT PATERNAL TRANSMISSION OF 15Q11-13-LINKED NONDELETION ANGELMAN SYNDROME LEADS TO PHENOTYPIC-EXPRESSION
    WAGSTAFF, J
    KNOLL, JHM
    GLATT, KA
    SHUGART, YY
    SOMMER, A
    LALANDE, M
    [J]. NATURE GENETICS, 1992, 1 (04) : 291 - 294
  • [26] WAGSTAFF J, 1991, AM J HUM GENET, V49, P330