PMID- 10453196
OWN - NLM
STAT- MEDLINE
DCOM- 19990901
LR  - 20211203
IS  - 1328-8067 (Print)
IS  - 1328-8067 (Linking)
VI  - 41
IP  - 4
DP  - 1999 Aug
TI  - Molecular analysis and diagnosis in Japanese patients with Wilson's disease.
PG  - 409-13
AB  - BACKGROUND: Wilson's disease is characterized by the toxic accumulation of copper
      in the liver, brain, cornea and other organs. It is caused by both impaired
      excretion via the bile and impaired incorporation of copper into ceruloplasmin in
      the liver. The Wilson's disease gene (ATP7B) has been cloned as a putative
      copper-transporting P-type ATPase gene. We therefore analysed mutations of ATP7B 
      in Japanese patients with Wilson's disease. METHODS: Twenty-three Japanese
      patients with Wilson's disease were investigated. In all patients, the ATP7B
      coding sequence, including exon-intron junctions, was analysed by restriction
      endonuclease digestion, mutation detected enhancement gel electrophoresis and/or 
      direct sequencing analysis of amplified fragments. RESULTS: Thirteen mutations
      were identified, including seven missense mutations, four detections, one
      insertion and one exon skipping in the coding region. The most common mutations
      were 2874deletion(del)C in exon 13 and arginine (Arg)778 leucine (Leu) in exon 8.
      DISCUSSION: None of the observed mutations, except for 2302insertion(ins)C, have 
      been previously detected in either European or North American patients. We
      conclude that the mutation spectrum of Wilson's disease may thus indicate a
      population-dependent pattern. Based on the population-dependent manner of the
      occurrence of ATP7B gene mutations, it may be possible to establish a molecular
      diagnosis system. A molecular diagnosis system is considered to be very effective
      for making a definitive diagnosis in very young patients and for also detecting
      carriers.
FAU - Shimizu, N
AU  - Shimizu N
AD  - Second Department of Pediatrics, Toho University School of Medicine, Tokyo,
      Japan. norikazu@med.toho-u.ac.jp
FAU - Nakazono, H
AU  - Nakazono H
FAU - Takeshita, Y
AU  - Takeshita Y
FAU - Ikeda, C
AU  - Ikeda C
FAU - Fujii, H
AU  - Fujii H
FAU - Watanabe, A
AU  - Watanabe A
FAU - Yamaguchi, Y
AU  - Yamaguchi Y
FAU - Hemmi, H
AU  - Hemmi H
FAU - Shimatake, H
AU  - Shimatake H
FAU - Aoki, T
AU  - Aoki T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Australia
TA  - Pediatr Int
JT  - Pediatrics international : official journal of the Japan Pediatric Society
JID - 100886002
RN  - 0 (Carrier Proteins)
RN  - 0 (Cation Transport Proteins)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
RN  - EC 7.2.2.8 (ATP7B protein, human)
RN  - EC 7.2.2.8 (Copper-Transporting ATPases)
SB  - IM
MH  - Adenosine Triphosphatases/*genetics
MH  - Adult
MH  - Asians/*genetics
MH  - Carrier Proteins/*genetics
MH  - *Cation Transport Proteins
MH  - Child
MH  - Copper-Transporting ATPases
MH  - DNA Mutational Analysis
MH  - Female
MH  - Frameshift Mutation
MH  - Gene Deletion
MH  - Hepatolenticular Degeneration/diagnosis/ethnology/*genetics
MH  - Humans
MH  - Japan
MH  - Male
MH  - Mutagenesis, Insertional
MH  - *Mutation
MH  - Mutation, Missense
MH  - Pedigree
MH  - Polymerase Chain Reaction
EDAT- 1999/08/24 00:00
MHDA- 1999/08/24 00:01
CRDT- 1999/08/24 00:00
PHST- 1999/08/24 00:00 [pubmed]
PHST- 1999/08/24 00:01 [medline]
PHST- 1999/08/24 00:00 [entrez]
AID - 10.1046/j.1442-200x.1999.01092.x [doi]
PST - ppublish
SO  - Pediatr Int. 1999 Aug;41(4):409-13. doi: 10.1046/j.1442-200x.1999.01092.x.