IDENTIFICATION OF A COMMON MUTATION IN THE CARNITINE PALMITOYLTRANSFERASE II GENE IN FAMILIAL RECURRENT MYOGLOBINURIA PATIENTS

被引：169
作者：
TARONI, F
VERDERIO, E
DWORZAK, F
WILLEMS, PJ
CAVADINI, P
DIDONATO, S
机构：
[1] IST NAZL NEUROL CARLO BESTA,DIV STUDIO MALATTIE NEUROMUSCOLARI,I-20133 MILAN,ITALY
[2] UNIV INSTELLING ANTWERP,DEPT MED GENET,B-2610 WILRIJK,BELGIUM
来源：
NATURE GENETICS | 1993年 / 4卷 / 03期
关键词：
D O I：
10.1038/ng0793-314
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
Carnitine palmitoyltransferase (CPT) II deficiency is the most common inherited disorder of lipid metabolism affecting skeletal muscle. We have identified a missense mutation (Ser113Leu) in one patient with the classical muscular symptomatology. Transfection experiments in COS cells demonstrate that the mutation drastically depresses the catalytic activity of CPT II. The mutation results in normal synthesis but a markedly reduced steady-state level of the protein, indicating decreased stability of mutant CPT II. The Ser113Leu mutation is the most frequent cause of CPT II deficiency. The mutation can be detected easily by restriction analysis enabling molecular diagnosis of most patients and identification of heterozygous carriers.
引用
收藏
页码：314 / 319
页数：6
相关论文
共 37 条
[11]  
Demaugre F., Et al., Hepatic and muscular presentations of carnitine palmitoyltransferase deficiency: Two distinct entities, Pediatr. Res, 24, pp. 308-311, (1988)
[12]  
DiDonato S., Et al., Heterogeneity of carnitine-palmitoyltransferase deficiency, J. Neurol. Sci, 50, pp. 207-215, (1981)
[13]  
Demaugre F., Et al., Infantile form of carnitine palmitoyltransferase II deficiency with hepatomuscular symptoms and sudden death. Physiopathological approach to carnitine palmitoyltransferase II deficiencies, J. Clin. Invest, 87, pp. 859-864, (1991)
[14]  
Zinn A.B., Hoppel C.L., An unusual form of carnitine palmitoyltransferase B (CPT-B) deficiency associated with neonatal cardiomyopathy and renal dysorganogenesis, Am. J. Hum. Genet, 49, (1991)
[15]  
Witt D.R., Et al., Carnitine palmitoyl transferase-type 2 deficiency: Two new cases and successful prenatal diagnosis, Am. J. Hum. Genet, 49, (1991)
[16]  
Hug G., Bove K.E., Soukup S., Lethal neonatal multiorgan deficiency of carnitine palmitoyltransferase II, New Engl. J. Med, 325, pp. 1862-1864, (1991)
[17]  
Taroni F., Et al., Biochemical and molecular studies of carnitine palmitoyltransferase II deficiency with hepatocardiomyopathic presentation, New Developments in Fatty Acid Oxidation, pp. 521-531, (1992)
[18]  
Finocchiaro G., Et al., cDNA cloning, sequence analysis and chromosomal localization of human carnitine palmitoyltransferase, Proc. Natn. Acad. Sci. U.S.A, 88, pp. 661-665, (1991)
[19]  
Minoletti F., Et al., Localization of the human gene for carnitine palmitoyltransferase to 1p13-p11 by non-radioactive in situ hybridization, Genomics, 13, pp. 1372-1374, (1992)
[20]  
Taroni F., Et al., Molecular characterization of inherited carnitine palmitoyltransferase II deficiency, Proc. Natn. Acad. Sci. U.S.A, 89, pp. 8429-8433, (1992)
1234