Prader-Willi syndrome is caused by disruption of the SNRPN gene

被引:52
作者
Kuslich, CD
Kobori, JA
Mohapatra, G
Gregorio-King, C
Donlon, TA
机构
[1] Kapiolani Hlth Res Inst, Mol & Cytogenet Lab, Honolulu, HI USA
[2] So Calif Permanente Med Grp, Dept Pediat, San Jose, CA USA
[3] Univ Calif San Francisco, San Francisco, CA 94143 USA
[4] Univ Hawaii Manoa, Dept Genet & Mol Biol, Honolulu, HI 96822 USA
关键词
D O I
10.1086/302177
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
A Prader-Willi syndrome patient is described who has a de novo balanced translocation, (4;15)(q27;q11.2)pat, with breakpoints lying between SNRPN exons 2 and 3. Parental-origin studies indicate that there is no uniparental disomy and no apparent deletion. This patient expresses ZNF127, SNRPN exons 1 and 2, IPW, and D15S227E (PAR1) but does not express either SNRPN exons 3 and 4 or D15S226E (PARS), as assayed by reverse transcription-PCR, of peripheral blood cells. Methylation studies showed normal biparental patterns of inheritance of loci DN34/ZNF127, D15S63, and SNRPN exon 1. Results for this patient and that reported by Sun et al. support the contention that an intact genomic region and/or transcription of SNRPN exons 2 and 3 play a pivotal role in the manifestations of the major clinical phenotype in Prader-Willi syndrome.
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页码:70 / 76
页数:7
相关论文
共 26 条
[1]   INHERITED MICRODELETIONS IN THE ANGELMAN AND PRADER-WILLI SYNDROMES DEFINE AN IMPRINTING CENTER ON HUMAN-CHROMOSOME-15 [J].
BUITING, K ;
SAITOH, S ;
GROSS, S ;
DITTRICH, B ;
SCHWARTZ, S ;
NICHOLLS, RD ;
HORSTHEMKE, B .
NATURE GENETICS, 1995, 9 (04) :395-400
[2]  
BUTLER MG, 1983, LANCET, V1, P1285
[3]  
Cassidy S. B., 1996, American Journal of Human Genetics, V59, pA21
[4]   SEPARATION OF LARGE DNA-MOLECULES BY CONTOUR-CLAMPED HOMOGENEOUS ELECTRIC-FIELDS [J].
CHU, G ;
VOLLRATH, D ;
DAVIS, RW .
SCIENCE, 1986, 234 (4783) :1582-1585
[5]   Balanced translocation 46,XY,t(2;15)(q37.2;q11.2) associated with atypical Prader-Willi syndrome [J].
Conroy, JM ;
Grebe, TA ;
Becker, LA ;
Tsuchiya, K ;
Nicholls, RD ;
Buiting, K ;
Horsthemke, B ;
Cassidy, SB ;
Schwartz, S .
AMERICAN JOURNAL OF HUMAN GENETICS, 1997, 61 (02) :388-394
[6]  
CRACOPOLI NC, 1997, CURRENT PROTOCOLS HU
[7]   CHARACTERIZATION OF A METHYLATION IMPRINT IN THE PRADER-WILLI-SYNDROME CHROMOSOME REGION [J].
DITTRICH, B ;
BUITING, K ;
GROSS, S ;
HORSTHEMKE, B .
HUMAN MOLECULAR GENETICS, 1993, 2 (12) :1995-1999
[8]   Imprint switching on human chromosome 15 may involve alternative transcripts of the SNRPN gene [J].
Dittrich, B ;
Buiting, K ;
Korn, B ;
Rickard, S ;
Buxton, J ;
Saitoh, S ;
Nicholls, RD ;
Poustka, A ;
Winterpacht, A ;
Zabel, B ;
Horsthemke, B .
NATURE GENETICS, 1996, 14 (02) :163-170
[9]   ISOLATION OF MOLECULAR PROBES ASSOCIATED WITH THE CHROMOSOME-15 INSTABILITY IN THE PRADER-WILLI SYNDROME [J].
DONLON, TA ;
LALANDE, M ;
WYMAN, A ;
BRUNS, G ;
LATT, SA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (12) :4408-4412
[10]   FUNCTIONAL IMPRINTING AND EPIGENETIC MODIFICATION OF THE HUMAN SNRPN GENE [J].
GLENN, CC ;
PORTER, KA ;
JONG, MTC ;
NICHOLLS, RD ;
DRISCOLL, DJ .
HUMAN MOLECULAR GENETICS, 1993, 2 (12) :2001-2005