SCREENING FOR FERROCHELATASE MUTATIONS - MOLECULAR HETEROGENEITY OF ERYTHROPOIETIC PROTOPORPHYRIA

被引:29
作者
WANG, XH
POHFITZPATRICK, M
TAKETANI, S
CHEN, T
PIOMELLI, S
机构
[1] NEW YORK MED COLL,DEPT DERMATOL,VALHALLA,NY 10595
[2] KANSAI MED UNIV,DEPT HYG,OSAKA,JAPAN
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 1994年 / 1225卷 / 02期
关键词
ERYTHROPOIETIC PROTOPORPHYRIA; FERROCHELATASE GENE; MUTATION;
D O I
10.1016/0925-4439(94)90077-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The DNA of 21 patients from 19 unrelated families with erythropoietic protoporphyria (EPP) were screened for the 6 ferrochelatase point mutations so far described. The mutation previously described by us (A >> T transversion at position - 3 of the donor site of intron 10, causing exon 10 skipping) was detected in two additional unrelated EPP patients: in these patients, cDNA lacking exon 10 was also detected. The mutation described by Nakahashi et al. as responsible for exon 2 skipping (C >> T transition at position -23 of the acceptor site of intron 1), although also observed in some normal individuals, was invariably observed in all EPP patients tested and may thus play some role in the pathogenesis of EPP. Thus, it does not appear that this mutation is the primary mechanism underlying exon 2 skipping. None of the other four previously described mutations were detected. These data demonstrate the heterogeneity of the ferrochelatase locus and of the genetic defect in EPP.
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收藏
页码:187 / 190
页数:4
相关论文
共 9 条
[1]  
BRENNER DA, 1992, AM J HUM GENET, V50, P1203
[2]   HUMAN ERYTHROPOIETIC PROTOPORPHYRIA - 2-POINT MUTATIONS IN THE FERROCHELATASE GENE [J].
LAMORIL, J ;
BOULECHFAR, S ;
DEVERNEUIL, H ;
GRANDCHAMP, B ;
NORDMANN, Y ;
DEYBACH, JC .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 181 (02) :594-599
[3]   MOLECULAR-CLONING AND SEQUENCE-ANALYSIS OF CDNA-ENCODING HUMAN FERROCHELATASE [J].
NAKAHASHI, Y ;
TAKETANI, S ;
OKUDA, M ;
INOUE, K ;
TOKUNAGA, R .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 173 (02) :748-755
[4]   THE MOLECULAR DEFECT OF FERROCHELATASE IN A PATIENT WITH ERYTHROPOIETIC PROTOPORPHYRIA [J].
NAKAHASHI, Y ;
FUJITA, H ;
TAKETANI, S ;
ISHIDA, N ;
KAPPAS, A ;
SASSA, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (01) :281-285
[5]  
NAKAHASHI Y, 1993, HUM GENET, V91, P303
[6]   STRUCTURE OF THE HUMAN FERROCHELATASE GENE - EXON INTRON GENE ORGANIZATION AND LOCATION OF THE GENE TO CHROMOSOME-18 [J].
TAKETANI, S ;
INAZAWA, J ;
NAKAHASHI, Y ;
ABE, T ;
TOKUNAGA, R .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1992, 205 (01) :217-222
[7]  
TODD DJ, 1993, BR J DERM S42, V129, P20
[8]   A NOVEL MUTATION IN ERYTHROPOIETIC PROTOPORPHYRIA - AN ABERRANT FERROCHELATASE MESSENGER-RNA CAUSED BY EXON SKIPPING DURING RNA SPLICING [J].
WANG, XH ;
POHFITZPATRICK, M ;
CARRIERO, D ;
OSTASIEWICZ, L ;
CHEN, T ;
TAKETANI, S ;
PIOMELLI, S .
BIOCHIMICA ET BIOPHYSICA ACTA, 1993, 1181 (02) :198-200
[9]   ASSIGNMENT OF THE HUMAN FERROCHELATASE GENE (FECH) AND A LOCUS FOR PROTOPORPHYRIA TO CHROMOSOME 18Q22 [J].
WHITCOMBE, DM ;
CARTER, NP ;
ALBERTSON, DG ;
SMITH, SJ ;
RHODES, DA ;
COX, TM .
GENOMICS, 1991, 11 (04) :1152-1154