PMID- 10519994
OWN - NLM
STAT- MEDLINE
DCOM- 19991119
LR  - 20190705
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 106
IP  - 4
DP  - 1999 Sep
TI  - A novel mutation of delta-aminolaevulinate dehydratase in a healthy child with
      12% erythrocyte enzyme activity.
PG  - 931-7
AB  - Cloning, expression and phenotype studies of the defective gene for
      delta-aminolaevulinate dehydratase (ALAD) in a family with an asymptomatic girl
      who had ALAD deficiency were carried out. The proband was identified by neonatal 
      ALAD screening, and had erythrocyte ALAD activity at 12% of the normal control.
      She was heterozygous for ALAD deficiency, which was inherited from her father.
      Nucleotide sequence analysis of the cloned ALAD cDNA revealed C36 to G and T168
      to C mutations on the same allele. The former mutation resulted in F12L
      substitution, whereas the latter was a silent mutation. All family members who
      had decreased ALAD activity had the same mutation. Expression of the mutant ALAD 
      cDNA in Chinese hamster ovary cells produced an ALAD protein without significant 
      enzyme activity. Additionally, the mutant ALAD cDNA which encodes F12L
      substitution produced an aberrant migration pattern in polyacrylamide gel
      electrophoresis under denaturing conditions. This finding probably reflects an
      abnormal folding of the F12L protein, since the mutation occurred in the alpha1
      helix of the N-terminal arm of the enzyme, which is involved in the extensive
      quaternary interactions among the subunits. This is also the first report of ALAD
      gene mutation in an asymptomatic subject.
FAU - Akagi, R
AU  - Akagi R
AD  - Faculty of Health and Welfare Science, Okayama Prefectural University, Soja-shi, 
      Japan.
FAU - Yasui, Y
AU  - Yasui Y
FAU - Harper, P
AU  - Harper P
FAU - Sassa, S
AU  - Sassa S
LA  - eng
GR  - DK-32890/DK/NIDDK NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (DNA, Complementary)
RN  - 0 (Porphyrins)
RN  - EC 4.2.1.24 (Porphobilinogen Synthase)
SB  - IM
MH  - DNA, Complementary/analysis
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Erythrocytes/*enzymology
MH  - Female
MH  - Humans
MH  - Male
MH  - Mutation/*genetics
MH  - Pedigree
MH  - Porphobilinogen Synthase/deficiency/*genetics/urine
MH  - Porphyrins/metabolism
EDAT- 1999/10/16 00:00
MHDA- 1999/10/16 00:01
CRDT- 1999/10/16 00:00
PHST- 1999/10/16 00:00 [pubmed]
PHST- 1999/10/16 00:01 [medline]
PHST- 1999/10/16 00:00 [entrez]
AID - bjh1647 [pii]
AID - 10.1046/j.1365-2141.1999.01647.x [doi]
PST - ppublish
SO  - Br J Haematol. 1999 Sep;106(4):931-7. doi: 10.1046/j.1365-2141.1999.01647.x.