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Title: Human triosephosphate isomerase deficiency resulting from mutation of Phe-240

Abstract

Triosephosphate isomerase (TPI; D-glyceraldehyde-3-phosphate ketolisomerase [E.C.5.3.1.1]) deficiency is an autosomal recessive disorder that typically results in chronic, nonspherocytic hemolytic anemia and in neuromuscular impairment. The molecular basis of this disease was analyzed for one Hungarian family and for two Australian families by localizing the defects in TPI cDNA and by determining how each defect affects TPI gene expression. The Hungarian family is noteworthy in having the first reported case of an individual, A. Jo., who harbors two defective TPI alleles but who does not manifest neuromuscular disabilities. This family was characterized by two mutations that have never been described. One is a missense mutation within codon 240 (TTC [Phe][r arrow]CTC [Leu]), which creates a thermolabile protein, as indicated by the results of enzyme activity assays using cell extracts. This substitution, which changes a phylogenetically conserved amino acid, may affect enzyme activity by dusrupting intersubunit contacts or substrate binding, as deduced from enzyme structural studies. The other mutation has yet to be localized but reduces the abundance of TPI mRNA 10--20-fold. Each of the Australian families was characterized by a previously described mutation within codon 104 (GAG [Glu][r arrow]GAC [Asp]), which also results in thermolabile protein. 49 refs., 6 figs., 1more » tab.« less

Authors:
; ;  [1];  [2];  [3];  [4]
  1. Roswell Park Cancer Inst., Buffalo, NY (United States)
  2. Univ. of Sheffield (United Kingdom)
  3. National Inst. of Hematology and Blood Transfusion, Budapest (Hungary)
  4. Children's Hospital, Sydney (Australia)
Publication Date:
OSTI Identifier:
6180545
Resource Type:
Journal Article
Journal Name:
American Journal of Human Genetics; (United States)
Additional Journal Information:
Journal Volume: 52:6; Journal ID: ISSN 0002-9297
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ANEMIAS; GENE MUTATIONS; ISOMERASES; STRUCTURE-ACTIVITY RELATIONSHIPS; NERVOUS SYSTEM DISEASES; AMINO ACID SEQUENCE; DISEASES; GENE REGULATION; HEREDITARY DISEASES; LEUCINE; MOLECULAR STRUCTURE; MUSCLES; PHENYLALANINE; AMINO ACIDS; CARBOXYLIC ACIDS; ENZYMES; HEMIC DISEASES; MUTATIONS; ORGANIC ACIDS; ORGANIC COMPOUNDS; PROTEINS; SYMPTOMS; 550400* - Genetics

Citation Formats

Chang, Minling, Wu, Xiaoyun, Maquat, L E, Artymiuk, P J, Hollan, S, and Lammi, A. Human triosephosphate isomerase deficiency resulting from mutation of Phe-240. United States: N. p., 1993. Web.
Chang, Minling, Wu, Xiaoyun, Maquat, L E, Artymiuk, P J, Hollan, S, & Lammi, A. Human triosephosphate isomerase deficiency resulting from mutation of Phe-240. United States.
Chang, Minling, Wu, Xiaoyun, Maquat, L E, Artymiuk, P J, Hollan, S, and Lammi, A. Tue . "Human triosephosphate isomerase deficiency resulting from mutation of Phe-240". United States.
@article{osti_6180545,
title = {Human triosephosphate isomerase deficiency resulting from mutation of Phe-240},
author = {Chang, Minling and Wu, Xiaoyun and Maquat, L E and Artymiuk, P J and Hollan, S and Lammi, A},
abstractNote = {Triosephosphate isomerase (TPI; D-glyceraldehyde-3-phosphate ketolisomerase [E.C.5.3.1.1]) deficiency is an autosomal recessive disorder that typically results in chronic, nonspherocytic hemolytic anemia and in neuromuscular impairment. The molecular basis of this disease was analyzed for one Hungarian family and for two Australian families by localizing the defects in TPI cDNA and by determining how each defect affects TPI gene expression. The Hungarian family is noteworthy in having the first reported case of an individual, A. Jo., who harbors two defective TPI alleles but who does not manifest neuromuscular disabilities. This family was characterized by two mutations that have never been described. One is a missense mutation within codon 240 (TTC [Phe][r arrow]CTC [Leu]), which creates a thermolabile protein, as indicated by the results of enzyme activity assays using cell extracts. This substitution, which changes a phylogenetically conserved amino acid, may affect enzyme activity by dusrupting intersubunit contacts or substrate binding, as deduced from enzyme structural studies. The other mutation has yet to be localized but reduces the abundance of TPI mRNA 10--20-fold. Each of the Australian families was characterized by a previously described mutation within codon 104 (GAG [Glu][r arrow]GAC [Asp]), which also results in thermolabile protein. 49 refs., 6 figs., 1 tab.},
doi = {},
journal = {American Journal of Human Genetics; (United States)},
issn = {0002-9297},
number = ,
volume = 52:6,
place = {United States},
year = {1993},
month = {6}
}