PMID- 10657149
OWN - NLM
STAT- MEDLINE
DCOM- 20000225
LR  - 20061115
IS  - 0890-8508 (Print)
IS  - 0890-8508 (Linking)
VI  - 13
IP  - 6
DP  - 1999 Dec
TI  - New mutations of the hydroxymethylbilane synthase gene in German patients with
      acute intermittent porphyria.
PG  - 443-7
AB  - Acute intermittent porphyria (AIP) is a low-penetrant, autosomal dominant
      disorder caused by decreased activity of hydroxymethylbilane synthase (HMBS; MIM 
      176 000), the third enzyme in the heme biosynthetic pathway. We report the first 
      molecular analysis of HMBS gene mutations in classical AIP patients of German
      origin. The HMBS gene of 5 German AIP patients was analysed by DGGE-screening and
      direct sequencing of amplified genomic DNA. Five different mutations including
      four novel mutations were found. Three of them are single base substitutions that
      affected exon 3 (R16C), exon 10 (V202L), and intron 13 (T to A, IVS13+2) The two 
      remaining mutations are frameshifts which produce a stop codon (del GA in exon 6 
      and insA in exon 14). These mutations are likely to be responsible for the
      decrease in HMBS activity found in both erythrocytes and non-erythroid cell lines
      (lymphocytes). Our results demonstrate the allelic heterogeneity of HMBS
      mutations in AIP patients of German origin.
CI  - Copyright 1999 Academic Press.
FAU - Gross, U
AU  - Gross U
AD  - Division of Clinical Biochemistry, Faculty of Medicine, Marburg, Federal Republic
      of Germany. Ulrich.Gross@avanea.de
FAU - Puy, H
AU  - Puy H
FAU - Doss, M
AU  - Doss M
FAU - Robreau, A M
AU  - Robreau AM
FAU - Nordmann, Y
AU  - Nordmann Y
FAU - Doss, M O
AU  - Doss MO
FAU - Deybach, J C
AU  - Deybach JC
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Mol Cell Probes
JT  - Molecular and cellular probes
JID - 8709751
RN  - EC 2.5.1.61 (Hydroxymethylbilane Synthase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Female
MH  - Humans
MH  - Hydroxymethylbilane Synthase/*genetics
MH  - Male
MH  - Mutation/*genetics
MH  - Pedigree
MH  - Porphyria, Acute Intermittent/*enzymology/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2000/02/05 09:00
MHDA- 2000/03/04 09:00
CRDT- 2000/02/05 09:00
PHST- 2000/02/05 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 2000/02/05 09:00 [entrez]
AID - 10.1006/mcpr.1999.0276 [doi]
AID - S0890850899902761 [pii]
PST - ppublish
SO  - Mol Cell Probes. 1999 Dec;13(6):443-7. doi: 10.1006/mcpr.1999.0276.