Unusual molecular findings in autosomal recessive spinal muscular atrophy

被引:35
作者
Matthijs, G
Schollen, E
Legius, E
Devriendt, K
Goemans, N
Kayserili, H
Apak, MY
Cassiman, JJ
机构
[1] KATHOLIEKE UNIV LEUVEN HOSP,DEPT PAEDIAT,B-3000 LOUVAIN,BELGIUM
[2] ISTANBUL UNIV,INST CHILD HLTH,DIV MED GENET,ISTANBUL 34390,TURKEY
关键词
spinal muscular atrophy; SMN gene; nonradioactive SSCP;
D O I
10.1136/jmg.33.6.469
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
All three types of autosomal recessive spinal muscular atrophy map to chromosome 5q11.2-q13.3 and are associated with deletions or mutations of the SMN (survival motor neurone) gene. The availability of a test to distinguish between the SMN gene and its nearly identical centromeric copy (C)BCD541 allows molecular diagnosis. We have analysed patients from 24 Belgian and 34 Turkish families for the presence or absence of a deletion in the SMN gene. A homozygous deletion in the SMN gene was seen in 90% of unrelated SMA patients. A non-radioactive SSCP assay allows for a semiquantitative analysis of the copy number of the centromeric and SMN genes. Hence, direct carrier detection has become feasible under certain conditions. We observed a phenotypically normal male, father of an SMA type I patient, presenting with only a single copy of the SMN gene and lacking both copies of the (C)BCD541 gene. This illustrates that a reduction of the total number of SMN and (C)BCD541 genes to a single SMN copy is compatible with normal life. In another SMA type I family, there is evidence for a de novo deletion of the centromeric gene in a normal sib. This observation illustrates the susceptibility of the SMA locus to de novo deletions and rearrangements.
引用
收藏
页码:469 / 474
页数:6
相关论文
共 11 条
[1]   SMN GENE DELETION IN VARIANT OF INFANTILE SPINAL MUSCULAR-ATROPHY [J].
BURGLEN, L ;
SPIEGEL, R ;
IGNATIUS, J ;
COBBEN, JM ;
LANDRIEU, P ;
LEFEBVRE, S ;
MUNNICH, A ;
MELKI, J .
LANCET, 1995, 346 (8970) :316-317
[2]  
CLERMONT O, 1994, AM J HUM GENET, V54, P687
[3]   A HUNGARIAN STUDY ON WERDNIG-HOFFMANN DISEASE [J].
CZEIZEL, A ;
HAMULA, J .
JOURNAL OF MEDICAL GENETICS, 1989, 26 (12) :761-763
[4]  
DEVRIENDT K, UNPUB ANN NEUROL
[5]   IDENTIFICATION AND CHARACTERIZATION OF A SPINAL MUSCULAR ATROPHY-DETERMINING GENE [J].
LEFEBVRE, S ;
BURGLEN, L ;
REBOULLET, S ;
CLERMONT, O ;
BURLET, P ;
VIOLLET, L ;
BENICHOU, B ;
CRUAUD, C ;
MILLASSEAU, P ;
ZEVIANI, M ;
LEPASLIER, D ;
FREZAL, J ;
COHEN, D ;
WEISSENBACH, J ;
MUNNICH, A ;
MELKI, J .
CELL, 1995, 80 (01) :155-165
[6]   MAPPING OF HUMAN MICROTUBULE-ASSOCIATED PROTEIN-1B IN PROXIMITY TO THE SPINAL MUSCULAR-ATROPHY LOCUS AT 5Q13 [J].
LIEN, LL ;
BOYCE, FM ;
KLEYN, P ;
BRZUSTOWICZ, LM ;
MENNINGER, J ;
WARD, DC ;
GILLIAM, TC ;
KUNKEL, LM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (17) :7873-7876
[7]   DELETIONS IN THE SURVIVAL MOTOR-NEURON GENE ON 5Q13 IN AUTOSOMAL RECESSIVE SPINAL MUSCULAR-ATROPHY [J].
RODRIGUES, NR ;
OWEN, N ;
TALBOT, K ;
IGNATIUS, J ;
DUBOWITZ, V ;
DAVIES, KE .
HUMAN MOLECULAR GENETICS, 1995, 4 (04) :631-634
[8]   PRENATAL-DIAGNOSIS OF SPINAL MUSCULAR-ATROPHY BY GENE DELETION ANALYSIS [J].
RODRIGUES, NR ;
CAMPBELL, L ;
OWEN, N ;
RODECK, CH ;
DAVIES, KE .
LANCET, 1995, 345 (8956) :1049-1049
[9]   THE GENE FOR NEURONAL APOPTOSIS INHIBITORY PROTEIN IS PARTIALLY DELETED IN INDIVIDUALS WITH SPINAL MUSCULAR-ATROPHY [J].
ROY, N ;
MAHADEVAN, MS ;
MCLEAN, M ;
SHUTLER, G ;
YARAGHI, Z ;
FARAHANI, R ;
BAIRD, S ;
BESNERJOHNSTON, A ;
LEFEBVRE, C ;
KANG, XL ;
SALIH, M ;
AUBRY, H ;
TAMAI, K ;
GUAN, XP ;
IOANNOU, P ;
CRAWFORD, TO ;
DEJONG, PJ ;
SURH, L ;
IKEDA, JE ;
KORNELUK, RG ;
MACKENZIE, A .
CELL, 1995, 80 (01) :167-178
[10]   REFINEMENT OF THE SPINAL MUSCULAR-ATROPHY LOCUS TO THE INTERVAL BETWEEN D5S435 AND MAP1B [J].
SOARES, VM ;
BRZUSTOWICZ, LM ;
KLEYN, PW ;
KNOWLES, JA ;
PALMER, DA ;
ASOKAN, S ;
PENCHASZADEH, GK ;
MUNSAT, TL ;
GILLIAM, TC .
GENOMICS, 1993, 15 (02) :365-371