PMID- 10515893
OWN - NLM
STAT- MEDLINE
DCOM- 19991122
LR  - 20131121
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 94
IP  - 8
DP  - 1999 Oct 15
TI  - The molecular basis of a case of gamma-glutamylcysteine synthetase deficiency.
PG  - 2890-4
AB  - Gamma-glutamylcysteine synthetase catalyzes the first step in glutathione
      synthesis. The enzyme consists of 2 subunits, heavy and light, with the heavy
      subunit serving as the catalytic subunit. A patient with hemolytic anemia and low
      red blood cell glutathione levels was found to have a deficiency of
      gamma-glutamylcysteine synthetase activity. Examination of cDNA from the patient 
      and her mother showed that she was homozygous and that her mother was
      heterozygous for a A-->T transversion at nt1109 producing a deduced amino acid
      change of His370Leu. The partial genomic structure of the catalytic subunit of
      gamma-glutamylcysteine synthetase (GLCLC) was determined, providing some
      intron/exon boundaries to make it possible to sequence an affected part of the
      coding region from genomic DNA. The 1109A-->T mutation was not present in the DNA
      of 38 normal subjects. In the course of these studies we found a diallelic
      polymorphism in nt +206 of an intron and another polymorphism that consisted of a
      duplication of a CAGC at cDNA nt1972-1975 in the 3' untranslated region. The 2
      polymorphisms were found to be only in partial linkage disequilibrium.
FAU - Beutler, E
AU  - Beutler E
AD  - Department of Molecular and Experimental Medicine, The Scripps Research
      Institute, La Jolla, CA 92037, USA.
FAU - Gelbart, T
AU  - Gelbart T
FAU - Kondo, T
AU  - Kondo T
FAU - Matsunaga, A T
AU  - Matsunaga AT
LA  - eng
SI  - GENBANK/AF118846
GR  - HL25552/HL/NHLBI NIH HHS/United States
GR  - RR00833/RR/NCRR NIH HHS/United States
PT  - Case Reports
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Codon)
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Complementary)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 6.3.2.2 (Glutamate-Cysteine Ligase)
RN  - GAN16C9B8O (Glutathione)
SB  - AIM
SB  - IM
MH  - Adolescent
MH  - Amino Acid Metabolism, Inborn Errors/blood/*genetics
MH  - Amino Acid Sequence
MH  - *Amino Acid Substitution
MH  - Anemia, Hemolytic/blood/enzymology/*genetics
MH  - Animals
MH  - Base Sequence
MH  - Catalytic Domain/genetics
MH  - Codon/genetics
MH  - Consanguinity
MH  - DNA Primers
MH  - DNA, Complementary/genetics
MH  - Erythrocytes/enzymology
MH  - Female
MH  - Genes
MH  - Glutamate-Cysteine Ligase/deficiency/*genetics
MH  - Glutathione/deficiency
MH  - Homozygote
MH  - Humans
MH  - Learning Disorders/blood/enzymology/*genetics
MH  - Lymphocytes/chemistry
MH  - Mice
MH  - Molecular Sequence Data
MH  - *Point Mutation
MH  - Rats
MH  - Recombinant Fusion Proteins/metabolism
MH  - Species Specificity
MH  - Transfection
EDAT- 1999/10/09 00:00
MHDA- 1999/10/09 00:01
CRDT- 1999/10/09 00:00
PHST- 1999/10/09 00:00 [pubmed]
PHST- 1999/10/09 00:01 [medline]
PHST- 1999/10/09 00:00 [entrez]
PST - ppublish
SO  - Blood. 1999 Oct 15;94(8):2890-4.