IDENTIFICATION OF A STOP MUTATION IN 5 FINNISH PATIENTS SUFFERING FROM HEREDITARY TYROSINEMIA TYPE-I

被引:36
作者
STLOUIS, M
LECLERC, B
LAINE, J
SALO, MK
HOLMBERG, C
TANGUAY, RM
机构
[1] UNIV LAVAL,CTR HOSP,CTR RECH,OGM,GENET CELLULAIRE & MOLEC LAB,ST FOY G1V 4G2,PQ,CANADA
[2] UNIV HELSINKI,CHILDRENS HOSP,HELSINKI,FINLAND
[3] UNIV TAMPERE,DEPT PEDIAT,TAMPERE,FINLAND
基金
英国医学研究理事会;
关键词
D O I
10.1093/hmg/3.1.69
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
Hereditary tyrosinemia type I is a metabolic disease caused by a deficiency of fumarylacetoacetate hydrolase (FAH, EC 3.7.1.2), the last enzyme in the catabolic pathway of tyrosine. The molecular basis of FAH deficiency was examined in five Finnish patients suffering from this severe metabolic disease. No immunoreactive FAH nor enzymatic activity were found in their liver. Direct sequencing of the 14 exons of the FAH gene showed a G to A transition, which predicts a change from tryptophan to a stop codon (TGG --> TGA) at position 262 (W262X). Four of the five patients examined were homozygous for the mutation. Allele specific oligonucleotide hybridization showed a predominance of the W262X mutation in Finland (9 of 10 alleles) and the absence of this mutant allele in patients from other parts of the world. The loss of a BsaJI restriction site in those patients may be used for diagnosis.
引用
收藏
页码:69 / 72
页数:4
相关论文
共 21 条
[1]   DIAGNOSTIC SINGLE-STRAND CONFORMATIONAL POLYMORPHISM, (SSCP) - A SIMPLIFIED NONRADIOISOTOPIC METHOD AS APPLIED TO A TAY-SACHS-B1 VARIANT [J].
AINSWORTH, PJ ;
SURH, LC ;
COULTERMACKIE, MB .
NUCLEIC ACIDS RESEARCH, 1991, 19 (02) :405-406
[2]  
DEBRAEKELEER M, 1990, AM J HUM GENET, V47, P302
[3]   MSPI RFLP IN THE HUMAN FUMARYLACETOACETATE HYDROLASE (FAH) GENE [J].
DEMERS, SI ;
TANGUAY, RM .
NUCLEIC ACIDS RESEARCH, 1991, 19 (24) :6971-6971
[4]   TAQI RFLP FOR THE HUMAN FUMARYLACETOACETATE HYDROLASE (FAH) GENE [J].
DEMERS, SI ;
PHANEUF, D ;
TANGUAY, RM .
NUCLEIC ACIDS RESEARCH, 1991, 19 (06) :1352-1352
[5]  
DEMERS SI, 1991, NUCLEIC ACIDS RES, V19, P1965
[6]   MUTATIONS OF THE FUMARYLACETOACETATE HYDROLASE GENE IN 4 PATIENTS WITH TYROSINEMIA, TYPE-I [J].
GROMPE, M ;
ALDHALIMY, M .
HUMAN MUTATION, 1993, 2 (02) :85-93
[7]  
KVITTINGEN EA, 1986, SCAND J CLIN LAB INV, V46, P27
[8]   CHARACTERIZATION OF THE HUMAN FUMARYLACETOACETATE HYDROLASE GENE AND IDENTIFICATION OF A MISSENSE MUTATION ABOLISHING ENZYMATIC-ACTIVITY [J].
LABELLE, Y ;
PHANEUF, D ;
LECLERC, B ;
TANGUAY, RM .
HUMAN MOLECULAR GENETICS, 1993, 2 (07) :941-946
[9]  
LABERGE C, 1969, AM J HUM GENET, V21, P36
[10]   ENZYMIC DEFECTS IN HEREDITARY TYROSINEMIA [J].
LINDBLAD, B ;
LINDSTEDT, S ;
STEEN, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1977, 74 (10) :4641-4645