PMID- 10502788
OWN - NLM
STAT- MEDLINE
DCOM- 19991007
LR  - 20061115
IS  - 1098-1004 (Electronic)
IS  - 1059-7794 (Linking)
VI  - 14
IP  - 4
DP  - 1999 Oct
TI  - Acute intermittent porphyria: characterization of two novel mutations in the
      porphobilinogen deaminase gene, one amino acid deletion (453-455delAGC) and one
      splicing aceptor site mutation (IVS8-1G>T).
PG  - 355
AB  - A partial deficiency of Porphobilinogen deaminase (PBG-D) is responsible for
      acute intermittent porphyria (AIP). AIP is inherited in an autosomal dominant
      fashion, and the prevalence in the Argentinean population is about 1:125,000.
      Here, two new mutations and three previously reported were found in the PBG-D
      gene in 12 Argentinean AIP patients corresponding to 5 different families. To
      screen for AIP mutations in symptomatic patients, genomic DNA isolated was
      amplified in 2 Multiplex PCR reactions, then all coding exons and flanking
      intronic regions were sequenced. The new mutations are 453-455delAGC in exon 9
      which results in the loss of an alanine residue at position 152, and one new
      point mutation in the splicing aceptor site in the last position of intron 8
      (IVS8-1G>T) which leds to a 15 bp deletion because a cryptic site (first AG
      upstream) is used. Both mutations produce amino acid deletion without frameshift 
      effect. To further characterize the 453-455delAGC mutation, the pKK-PBGD
      construct for the mutant allele was expressed in E. coli, the enzymatic activity 
      of the recombinant protein was 1.3% of the mean level expressed by the normal
      allele. Finally, three missense mutations, previously reported, were identified
      in three unrelated families.
CI  - Copyright 1999 Wiley-Liss, Inc.
FAU - De Siervi, A
AU  - De Siervi A
AD  - Centro de Investigaciones sobre Porfirinas y Porfirias, CONICET and Fac. Ciencias
      Exactas y Naturales, University of Buenos Aires, Argentina.
FAU - Mendez, M
AU  - Mendez M
FAU - Parera, V E
AU  - Parera VE
FAU - Varela, L
AU  - Varela L
FAU - Batlle, A M
AU  - Batlle AM
FAU - Rossetti, M V
AU  - Rossetti MV
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - EC 2.5.1.61 (Hydroxymethylbilane Synthase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Escherichia coli/enzymology
MH  - Female
MH  - Humans
MH  - Hydroxymethylbilane Synthase/biosynthesis/*genetics/metabolism
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Porphyrias/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 1999/09/30 00:00
MHDA- 1999/09/30 00:01
CRDT- 1999/09/30 00:00
PHST- 1999/09/30 00:00 [pubmed]
PHST- 1999/09/30 00:01 [medline]
PHST- 1999/09/30 00:00 [entrez]
AID - 10.1002/(SICI)1098-1004(199910)14:4<355::AID-HUMU19>3.0.CO;2-T [pii]
AID - 10.1002/(SICI)1098-1004(199910)14:4<355::AID-HUMU19>3.0.CO;2-T [doi]
PST - ppublish
SO  - Hum Mutat. 1999 Oct;14(4):355. doi:
      10.1002/(SICI)1098-1004(199910)14:4<355::AID-HUMU19>3.0.CO;2-T.