A biochemical, genetic, and clinical survey of autosomal recessive limb girdle muscular dystrophies in Turkey

被引:92
作者
Dincer, P
Leturcq, F
Richard, I
Piccolo, F
Yalnizoglu, D
deToma, C
Akcoren, Z
Broux, O
Deburgrave, N
Brenguier, L
Roudaut, C
Urtizberea, JA
Jung, D
Tan, E
Jeanpierre, M
Campbell, KP
Kaplan, JC
Beckmann, JS
Topaloglu, H
机构
[1] HACETTEPE UNIV, FAC MED, DEPT MED BIOL, TR-06100 ANKARA, TURKEY
[2] HACETTEPE UNIV, FAC MED, DEPT PEDIAT NEUROL, TR-06100 ANKARA, TURKEY
[3] HACETTEPE UNIV, FAC MED, DEPT PEDIAT PATHOL, TR-06100 ANKARA, TURKEY
[4] HACETTEPE UNIV, FAC MED, DEPT NEUROL, TR-06100 ANKARA, TURKEY
[5] UNIV PARIS, HOP COCHIN, SERV BIOCHIM & GENET MOL, F-75252 PARIS, FRANCE
[6] UNIV PARIS, HOP COCHIN, INSERM 129, F-75252 PARIS, FRANCE
[7] AFM, MYOBANK, EVRY, FRANCE
[8] UNIV IOWA, COLL MED, HOWARD HUGHES MED INST, DEPT PHYSIOL & BIOPHYS, IOWA CITY, IA 52242 USA
关键词
D O I
10.1002/ana.410420214
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Autosomal recessive limb girdle muscular dystrophy (LGMD2) is a clinically and genetically heterogenous group of diseases involving at least six different loci, Five genes have already been identified: calpain-3 at LGMD2A (15q15), and four members of the sarcoglycan (SG) complex, alpha-SG at LGMD2D (17q21), beta-SG at LGMD2E (4q12), gamma-SG at LGMD2C (13q12), and delta-SG at LGMD2F (5q3S-q34). The gene product at LGMD2B (2p13-p16) is still unknown and at least one other gene is still unmapped, We investigated 20 Turkish families (18 consanguineous) diagnosed as having LGMD2, Most of our patients had onset of symptoms before age 10. The phenotypes varied from severe to benign. We analyzed the SG complex by immunofluorescence and/or western blot, Genotyping was performed using markers defining the six known loci and the suspected genes were screened for mutations, Six of 17 index cases showed deficiency of the SG complex, by immunofluorescence and/or western blot, Seven cases involved one of the known genes of the Se; complex (alpha, 2; beta, 1; and gamma, 4 cases), and five mutations were documented in the alpha- and gamma-SG genes. After linkage analysis, 10 families were characterized as having LGMD2A (calpain-3 deficiency), and all mutations were eventually identified, One family was classified as having LGMD2B and 1 family that has normal SGs was linked to the chromosome 5q33-q34 locus (LGMD2F), In 1 family there was no linkage to any of the known LGMD2 loci, It appears that in Turkey, there is a broad spectrum of genes and defects involved in LGMD2, It may be possible to correlate genotype to phenotype in LGMD2. All severe cases belonged to the gamma-SG-deficiency group, Nine calpain-3-deficient cases had intermediate and 1 had moderate clinical courses, The LGMD2B patient had a moderate clinical expression whereas the LGMD2F case was truly benign.
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页码:222 / 229
页数:8
相关论文
共 44 条
[1]  
ALLAMAND V, 1995, AM J HUM GENET, V56, P1417
[2]   ADHALIN GENE POLYMORPHISM [J].
ALLAMAND, V ;
LETURCQ, F ;
PICCOLO, F ;
JEANPIERRE, M ;
AZIBI, K ;
ROBERDS, SL ;
LIM, LE ;
CAMPBELL, KP ;
BECKMANN, JS ;
KAPLAN, JC .
HUMAN MOLECULAR GENETICS, 1994, 3 (12) :2269-2269
[3]  
AZIBI K, 1993, HUM MOL GENET, V2, P1423
[4]   A GENE FOR AUTOSOMAL RECESSIVE LIMB-GIRDLE MUSCULAR-DYSTROPHY MAPS TO CHROMOSOME 2P [J].
BASHIR, R ;
STRACHAN, T ;
KEERS, S ;
STEPHENSON, A ;
MAHJNEH, I ;
MARCONI, G ;
NASHEF, L ;
BUSHBY, KMD .
HUMAN MOLECULAR GENETICS, 1994, 3 (03) :455-457
[5]  
Beaudet AL, 1996, HUM MUTAT, V8, P197
[6]  
BECKMANN JS, 1991, CR ACAD SCI III-VIE, V312, P141
[7]   Advances in the molecular genetics of the limb-girdle type of autosomal recessive progressive muscular dystrophy [J].
Beckmann, JS ;
Bushby, KMD .
CURRENT OPINION IN NEUROLOGY, 1996, 9 (05) :389-393
[8]   LINKAGE OF TUNISIAN AUTOSOMAL RECESSIVE DUCHENNE-LIKE MUSCULAR-DYSTROPHY TO THE PERICENTROMERIC REGION OF CHROMOSOME 13Q [J].
BENOTHMANE, K ;
BENHAMIDA, M ;
PERICAKVANCE, MA ;
BENHAMIDA, C ;
BLEL, S ;
CARTER, SC ;
BOWCOCK, AM ;
PETRUKHIN, K ;
GILLIAM, TC ;
ROSES, AD ;
HENTATI, F ;
VANCE, JM .
NATURE GENETICS, 1992, 2 (04) :315-317
[9]  
Beutler E, 1996, HUM MUTAT, V8, P203, DOI 10.1002/(SICI)1098-1004(1996)8:3<203::AID-HUMU1>3.3.CO
[10]  
2-C