PMID- 10944860
OWN - NLM
STAT- MEDLINE
DCOM- 20000901
LR  - 20051117
IS  - 1434-5161 (Print)
IS  - 1434-5161 (Linking)
VI  - 45
IP  - 4
DP  - 2000
TI  - Two deletion mutations in the hydroxymethylbilane synthase gene in two unrelated 
      Japanese patients with acute intermittent porphyria.
PG  - 263-8
AB  - Acute intermittent porphyria (AIP) is an autosomal dominant inherited disease 
      caused by a decreased activity of hydroxymethylbilane synthase (HMBS). Regarding 
      the abnormalities of the HMBS gene, many different mutations have been reported 
      worldwide; however, few families from Japan have been studied. In this work, we 
      investigated the presence of mutations in two unrelated Japanese patients with 
      AIP. Mutational analysis was performed using the polymerase chain reaction-single 
      strand conformation polymorphism (SSCP) method, followed by DNA sequencing. 
      Reliable restriction enzyme cleavage assays were also established for the 
      pedigree analyses. Unique SSCP patterns were noted in exons 12 and 15 of the HMBS 
      gene. Sequencing revealed different mutations in each patient: a two-base 
      deletion of CT at nucleotide 730-731 (730delCT), and also a two-base deletion of 
      CA at position 982-983 (982delCA). Both of the deletion mutations lead to 
      truncated proteins with an abnormal C-terminus, which would be expected to 
      decrease the stability and/or activity of HMBS. Using the cleavage assays, we 
      were able to definitively identify gene carriers in the family. This study adds a 
      novel mutation to those that have been previously reported, and emphasizes that 
      molecular analysis would be very useful not only for the identification of 
      asymptomatic gene carriers in the family but also for the detection of ancestral 
      founders in porphyria families.
FAU - Maeda, N
AU  - Maeda N
AD  - Second Department of Internal Medicine, Faculty of Medicine, Tottori University, 
      Yonago, Japan. nmaeda@grape.med.tottori-u.ac.jp
FAU - Horie, Y
AU  - Horie Y
FAU - Adachi, K
AU  - Adachi K
FAU - Nanba, E
AU  - Nanba E
FAU - Kawasaki, H
AU  - Kawasaki H
FAU - Daimon, M
AU  - Daimon M
FAU - Kudo, Y
AU  - Kudo Y
FAU - Kondo, M
AU  - Kondo M
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Hum Genet
JT  - Journal of human genetics
JID - 9808008
RN  - EC 2.5.1.61 (Hydroxymethylbilane Synthase)
SB  - IM
MH  - Adult
MH  - Base Sequence
MH  - DNA Mutational Analysis
MH  - Female
MH  - Humans
MH  - Hydroxymethylbilane Synthase/*genetics
MH  - Male
MH  - Middle Aged
MH  - Pedigree
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single-Stranded Conformational
MH  - Porphyria, Acute Intermittent/*genetics
MH  - Sequence Deletion
EDAT- 2000/08/17 11:00
MHDA- 2000/09/09 11:01
CRDT- 2000/08/17 11:00
PHST- 2000/08/17 11:00 [pubmed]
PHST- 2000/09/09 11:01 [medline]
PHST- 2000/08/17 11:00 [entrez]
AID - 10.1007/s100380070038 [doi]
PST - ppublish
SO  - J Hum Genet. 2000;45(4):263-8. doi: 10.1007/s100380070038.