CHARACTERIZATION OF 3 MUTATIONS OF THE LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE IN ITALIAN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA

被引:26
作者
LELLI, N
GHISELLINI, M
GUALDI, R
TIOZZO, R
CALANDRA, S
GADDI, A
CIARROCCHI, A
ARCA, M
FAZIO, S
COVIELLO, DA
BERTOLINI, S
机构
[1] UNIV MODENA,IST PATOL GEN,VIA CAMPI 287,I-41100 MODENA,ITALY
[2] UNIV BOLOGNA,CATTEDRA GERONTOL,I-40126 BOLOGNA,ITALY
[3] UNIV ROME LA SAPIENZA,IST TERAPIA MED SISTEMAT,I-00185 ROME,ITALY
[4] UNIV GENOA,SERV PREVENZ ARTERIOSCLEROSI,I-16126 GENOA,ITALY
[5] UNIV GENOA,CATTEDRA GENET MED,I-16126 GENOA,ITALY
来源
ARTERIOSCLEROSIS AND THROMBOSIS | 1991年 / 11卷 / 02期
关键词
FAMILIAL HYPERCHOLESTEROLEMIA; SOUTHERN BLOTTING ANALYSIS; LOW DENSITY LIPOPROTEIN RECEPTOR GENE; ITALIAN FAMILIAL HYPERCHOLESTEROLEMIC PATIENTS;
D O I
10.1161/01.ATV.11.2.234
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Three gross rearrangements of the low density lipoprotein receptor (LDL-R) gene were recognized during a survey of 23 unrelated Italian subjects with familial hypercholesterolemia (FH). Restriction endonuclease data were obtained by Southern blotting and hybridization with exon-specific probes. Proband FH-29 is heterozygous for a 4-kb deletion, which eliminates exons 13 and 14. This mutation is similar to that previously reported by other investigators in one Italian homozygous and two British and Canadian heterozygous patients. Proband FH-30 is homozygous for a 5.5-kb insertion caused by a duplication of exons 16 and 17 of the LDL-R gene. LDL-R mRNA isolated from skin fibroblasts of FH-30 was found to be larger than normal mRNA (5.6 versus 5.3 kb), in concordance with the insertion of the 236 nucleotides corresponding to exons 16 and 17. Proband FH-44 was found to have > 25-kb deletion, which eliminates the first six exons and the promoter region of the gene. This is the first example of a deletion that eliminates the promoter as well as the ligand-binding domain of the LDL-R gene. In the skin fibroblasts of this patient, the level of LDL-R mRNA was approximately half that found in control fibroblasts. We designate the new mutations found in FH-30 and FH-44 as FH(Viterbo) and FH(Bologna-1), respectively, after the names of the Italian cities where the two patients were born.
引用
收藏
页码:234 / 243
页数:10
相关论文
共 41 条
[2]   IDENTIFICATION OF A DELETION IN THE LDL RECEPTOR GENE - A FINNISH TYPE OF MUTATION [J].
AALTOSETALA, K ;
GYLLING, H ;
MIETTINEN, T ;
KONTULA, K .
FEBS LETTERS, 1988, 230 (1-2) :31-34
[3]   FINNISH TYPE OF LOW-DENSITY LIPOPROTEIN RECEPTOR GENE MUTATION (FH-HELSINKI) DELETES EXONS ENCODING THE CARBOXY-TERMINAL PART OF THE RECEPTOR AND CREATES IN INTERNALIZATION-DEFECTIVE PHENOTYPE [J].
AALTOSETALA, K ;
HELVE, E ;
KOVANEN, PT ;
KONTULA, K .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 84 (02) :499-505
[4]  
ALLAIN CC, 1974, CLIN CHEM, V20, P470
[5]   NEW AMBER MUTATION IN A BETA-THALASSEMIC GENE WITH NONMEASURABLE LEVELS OF MUTANT MESSENGER-RNA INVIVO [J].
ATWEH, GF ;
BRICKNER, HE ;
ZHU, XX ;
KAZAZIAN, HH ;
FORGET, BG .
JOURNAL OF CLINICAL INVESTIGATION, 1988, 82 (02) :557-561
[6]   NONSENSE MUTATIONS IN THE HUMAN BETA-GLOBIN GENE AFFECT MESSENGER-RNA METABOLISM [J].
BASERGA, SJ ;
BENZ, EJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (07) :2056-2060
[7]   A RECEPTOR-MEDIATED PATHWAY FOR CHOLESTEROL HOMEOSTASIS [J].
BROWN, MS ;
GOLDSTEIN, JL .
SCIENCE, 1986, 232 (4746) :34-47
[8]  
BUCOLO G, 1973, CLIN CHEM, V19, P476
[9]  
CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2
[10]  
DAVIS CG, 1986, CELL, V45, P15, DOI 10.1016/0092-8674(86)90533-7