Two different mutations are responsible for Krabbe disease in the Druze and Moslem Arab populations in Israel

被引:52
作者
Rafi, MA
Luzi, P
Zlotogora, J
Wenger, DA
机构
[1] JEFFERSON MED COLL,DEPT MED MED GENET,PHILADELPHIA,PA 19107
[2] JEFFERSON MED COLL,DEPT BIOCHEM & MOLEC BIOL,PHILADELPHIA,PA 19107
[3] HADASSAH MED CTR,DEPT HUMAN GENET,IL-91120 JERUSALEM,ISRAEL
关键词
D O I
10.1007/BF02185759
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Infantile Krabbe disease is a severe, fatal autosomal recessive disorder resulting from the deficiency of galactocerebrosidase (GALC) activity. It is relatively common in two separate inbred communities in Israel. In the Druze community in Northern Israel and two Moslem Arab villages located near Jerusalem the incidence of Krabbe disease is about 1 in 100-150 live births. With our cloning of the GALC gene, mutation analysis of these populations was undertaken. The Moslem Arabs were homozygous for two mutations in the GALC gene; a T-to-C transition at cDNA position 1637 (counting from the A of the initiation codon), which is considered a polymorphism, and a G-to-A transition at position 1582, which changes the codon for aspartic acid to one for asparagine. The Druze patients are homozygous for a T-to-G transversion at position 1748, which changes the codon for isoleucine to one for serine. Expression studies confirmed the deleterious nature of these mutations. The development of a simple polymerase chain reaction (PCR) amplification and restriction enzyme digestion method to identify these alleles will lead to accurate carrier testing and improved genetic counseling for interested individuals in these communities.
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页码:304 / 308
页数:5
相关论文
共 16 条
[1]  
BACH G, 1993, AM J HUM GENET, V53, P330
[2]   OPTIMAL CONDITIONS FOR DIRECTLY SEQUENCING DOUBLE-STRANDED PCR PRODUCTS WITH SEQUENASE [J].
CASANOVA, JL ;
PANNETIER, C ;
JAULIN, C ;
KOURILSKY, P .
NUCLEIC ACIDS RESEARCH, 1990, 18 (13) :4028-4028
[3]   CLONING AND EXPRESSION OF CDNA-ENCODING HUMAN GALACTOCEREBROSIDASE, THE ENZYME-DEFICIENT IN GLOBOID-CELL LEUKODYSTROPHY [J].
CHEN, YQ ;
RAFI, MA ;
DEGALA, G ;
WENGER, DA .
HUMAN MOLECULAR GENETICS, 1993, 2 (11) :1841-1845
[4]   GALACTOCEREBROSIDASE FROM HUMAN URINE - PURIFICATION AND PARTIAL CHARACTERIZATION [J].
CHEN, YQ ;
WENGER, DA .
BIOCHIMICA ET BIOPHYSICA ACTA, 1993, 1170 (01) :53-61
[5]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159
[6]   THE CPG DINUCLEOTIDE AND HUMAN GENETIC-DISEASE [J].
COOPER, DN ;
YOUSSOUFIAN, H .
HUMAN GENETICS, 1988, 78 (02) :151-155
[7]  
HEINISCH U, 1995, AM J HUM GENET, V56, P51
[8]   STRUCTURE AND ORGANIZATION OF THE HUMAN GALACTOCEREBROSIDASE (GALC) GENE [J].
LUZI, P ;
RAFI, MA ;
WENGER, DA .
GENOMICS, 1995, 26 (02) :407-409
[9]   A LARGE DELETION TOGETHER WITH A POINT MUTATION IN THE GALC GENE IS A COMMON MUTANT ALLELE IN PATIENTS WITH INFANTILE KRABBE DISEASE [J].
RAFI, MA ;
LUZI, P ;
CHEN, YQ ;
WENGER, DA .
HUMAN MOLECULAR GENETICS, 1995, 4 (08) :1285-1289
[10]   DNA SEQUENCING WITH CHAIN-TERMINATING INHIBITORS [J].
SANGER, F ;
NICKLEN, S ;
COULSON, AR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1977, 74 (12) :5463-5467