PMID- 10407778
OWN - NLM
STAT- MEDLINE
DCOM- 19990923
LR  - 20190831
IS  - 0141-8955 (Print)
IS  - 0141-8955 (Linking)
VI  - 22
IP  - 4
DP  - 1999 Jun
TI  - 4-Aminobutyrate aminotransferase (GABA-transaminase) deficiency.
PG  - 414-27
AB  - 4-Aminobutyrate aminotransferase (GABA-transaminase, GABA-T, EC 2.6.1.19)
      deficiency (McKusick 137150), an inborn error of GABA degradation, has until now 
      been documented in only a single Flemish child. Compared to the other defects of 
      GABA degradation, succinic semialdehyde dehydrogenase (SSADH, EC 1.2.1.24)
      deficiency with > 150 patients (McKusick 271980) and pyridoxine-dependent
      seizures with > 100 patients ('putative' glutamic acid decarboxylase (GAD, EC
      4.1.1.15) deficiency; McKusick 266100), GABA-T deficiency is very rare. We
      present a summary of the clinical, biochemical, enzymatic and molecular findings 
      on the index proband, and a recently identified second patient, with GABA-T
      deficiency. The phenotype in both included psychomotor retardation, hypotonia,
      hyperreflexia, lethargy, refractory seizures and electroencephalographic
      abnormalities. In an effort to elucidate the molecular basis of GABA-T
      deficiency, we isolated and characterized a 1.5 kb cDNA encoding human GABA-T, in
      addition to a 41 kb genomic clone which encompassed the GABA-T coding region.
      Standard methods of cloning and sequencing revealed an A-to-G transition at
      nucleotide 754 of the coding region in lymphoblast cDNAs derived from the index
      proband. This mutation resulted in substitution of an invariant arginine at amino
      acid 220 by lysine. Expression of the mutant in E. coli, followed by isolation
      and enzymatic characterization of the recombinant protein, revealed an enzyme
      whose Vmax was reduced to 25% of wild-type activity. The patient and father were 
      heterozygous for this allele; the second allele in the patient remains
      unidentified. Genomic Southern analysis revealed that the second proband most
      likely harbours a deletion in the 3' region of the GABA-T gene.
FAU - Medina-Kauwe, L K
AU  - Medina-Kauwe LK
AD  - Institute for Genetic Medicine, University of California, Los Angeles, USA.
FAU - Tobin, A J
AU  - Tobin AJ
FAU - De Meirleir, L
AU  - De Meirleir L
FAU - Jaeken, J
AU  - Jaeken J
FAU - Jakobs, C
AU  - Jakobs C
FAU - Nyhan, W L
AU  - Nyhan WL
FAU - Gibson, K M
AU  - Gibson KM
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - J Inherit Metab Dis
JT  - Journal of inherited metabolic disease
JID - 7910918
RN  - 0 (DNA, Complementary)
RN  - EC 2.6.1.19 (4-Aminobutyrate Transaminase)
SB  - IM
MH  - 4-Aminobutyrate Transaminase/*deficiency/*genetics
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - DNA Mutational Analysis
MH  - DNA, Complementary
MH  - Humans
MH  - Molecular Sequence Data
RF  - 32
EDAT- 1999/07/17 00:00
MHDA- 1999/07/17 00:01
CRDT- 1999/07/17 00:00
PHST- 1999/07/17 00:00 [pubmed]
PHST- 1999/07/17 00:01 [medline]
PHST- 1999/07/17 00:00 [entrez]
AID - 10.1023/a:1005500122231 [doi]
PST - ppublish
SO  - J Inherit Metab Dis. 1999 Jun;22(4):414-27. doi: 10.1023/a:1005500122231.