Prenatal diagnosis of fragile X syndrome and the risk of expansion of a premutation

被引:11
作者
Kallinen, J
Heinonen, S [1 ]
Mannermaa, A
Ryynänen, M
机构
[1] Kuopio Univ Hosp, Dept Obstet & Gynecol, FIN-70211 Kuopio, Finland
[2] Kuopio Univ Hosp, Dept Clin Genet, FIN-70211 Kuopio, Finland
关键词
fragile X syndrome; genetic screening; prenatal diagnosis;
D O I
10.1034/j.1399-0004.2000.580204.x
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The aim of the present study was to evaluate prospectively the dynamics of the FMR1 gene. The risk of full mutation among pregnant women and the carriers, and the risk of expansion of a premutation allele to a full mutation were estimated. We identified 89 pregnant women with an expanded FMR1 gene seeking prenatal diagnosis. Amniocentesis or chorion villus sampling (CVS) was offered and a DNA test of the FMR1 gene was carried out in such pregnancies. The overall risk of full mutation among women (N = 21) with a repeat size between 60 and 80 was 4.8% (one fetus with mosaicism), and the risk of expansion of the premutation allele to a full mutation was 14% in those offspring to whom the premutation allele was transmitted. The risk of full mutation among the carriers (N = 13) with a repeat size between 81 and 100 was 61.5% (8/13), and the risk of expansion of a premutation allele to a full mutation was 89%. Only one case fell into the category of 101-200 repeats, and expansion to a full mutation was recorded. Fetuses of full mutation mothers inherited the larger allele in 64% (14/22) of the cases. The range of 40-59 repeats was safe: there were no fetal full mutations. The risk of full mutation was also low among the subjects with a repeat size between 60 and 80, whereas the risk increased significantly after 80 repeats. Maternal premutation size was positively correlated with the risk of having a full mutation offspring.
引用
收藏
页码:111 / 115
页数:5
相关论文
共 34 条
[1]   HUMAN AND MURINE FMR-1 - ALTERNATIVE SPLICING AND TRANSLATIONAL INITIATION DOWNSTREAM OF THE CGG-REPEAT [J].
ASHLEY, CT ;
SUTCLIFFE, JS ;
KUNST, CB ;
LEINER, HA ;
EICHLER, EE ;
NELSON, DL ;
WARREN, ST .
NATURE GENETICS, 1993, 4 (03) :244-251
[2]   Analysis of domains affecting intracellular localization of the FMRP protein [J].
Bardoni, B ;
Sittler, A ;
Shen, Y ;
Mandel, JL .
NEUROBIOLOGY OF DISEASE, 1997, 4 (05) :329-336
[3]   RAPID FRAGILE-X CARRIER SCREENING AND PRENATAL-DIAGNOSIS USING A NONRADIOACTIVE PCR TEST [J].
BROWN, WT ;
HOUCK, GE ;
JEZIOROWSKA, A ;
LEVINSON, FN ;
DING, XH ;
DOBKIN, C ;
ZHONG, N ;
HENDERSON, J ;
BROOKS, SS ;
JENKINS, EC .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1993, 270 (13) :1569-1575
[4]  
Cohen IL, 1996, AM J MED GENET, V64, P365, DOI 10.1002/(SICI)1096-8628(19960809)64:2<365::AID-AJMG26>3.3.CO
[5]  
2-P
[6]   Abnormal dendritic spines in fragile X knockout mice: Maturation and pruning deficits [J].
Comery, TA ;
Harris, JB ;
Willems, PJ ;
Oostra, BA ;
Irwin, SA ;
Weiler, IJ ;
Greenough, WT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (10) :5401-5404
[7]   The fragile X mental retardation protein is associated with poly(A)(+) mRNA in actively translating polyribosomes [J].
Corbin, F ;
Bouillon, M ;
Fortin, A ;
Morin, S ;
Rousseau, F ;
Khandjian, EW .
HUMAN MOLECULAR GENETICS, 1997, 6 (09) :1465-1472
[8]   A POINT MUTATION IN THE FMR-1 GENE ASSOCIATED WITH FRAGILE-X MENTAL-RETARDATION [J].
DEBOULLE, K ;
VERKERK, AJMH ;
REYNIERS, E ;
VITS, L ;
HENDRICKX, J ;
VANROY, B ;
VANDENBOS, F ;
DEGRAAFF, E ;
OOSTRA, BA ;
WILLEMS, PJ .
NATURE GENETICS, 1993, 3 (01) :31-35
[9]   THE FMR-1 PROTEIN IS CYTOPLASMIC, MOST ABUNDANT IN NEURONS AND APPEARS NORMAL IN CARRIERS OF A FRAGILE X PREMUTATION [J].
DEVYS, D ;
LUTZ, Y ;
ROUYER, N ;
BELLOCQ, JP ;
MANDEL, JL .
NATURE GENETICS, 1993, 4 (04) :335-340
[10]  
DOBKIN CS, 1991, LANCET, V338, P957