PMID- 10616841
OWN - NLM
STAT- MEDLINE
DCOM- 20000204
LR  - 20220409
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 11
IP  - 1
DP  - 2000 Jan
TI  - Novel mutations in thiazide-sensitive Na-Cl cotransporter gene of patients with
      Gitelman's syndrome.
PG  - 65-70
LID - 10.1681/ASN.V11165 [doi]
AB  - Gitelman's syndrome (GS) is an autosomal recessive disorder characterized by
      metabolic alkalosis, hypokalemia, hypomagnesemia, and hypocalciuria that has
      recently been reported to be linked to thiazide-sensitive Na-Cl cotransporter
      (TSC) gene mutations. In this study, possible mutations in the TSC gene of six
      Japanese patients clinically diagnosed with GS were investigated. Twenty-six
      exons encoding TSC were amplified by PCR and then completely sequenced by the
      direct sequencing method. Patient A showed a missense mutation of Arg 642 to Cys 
      on the paternal allele and a missense mutation of Val 578 to Met and a 2-bp
      deletion (nucleotide 2543-2544) on the maternal allele. This deletion results in 
      a frameshift that alters codon 837 to encode a stop signal rather than
      phenylalanine, and it is predicted to lead to loss of the latter half of the
      intracellular carboxy terminus. In the second family, two affected sisters,
      patients B and C, had a homozygous missense mutation of Thr 180 to Lys. Both of
      their parents, who are consanguineously married, have a heterozygous Thr180Lys
      mutation. Patient D has a homozygous mutation Thr180Lys, which is the same as the
      second family. Haplotype analysis indicates that patients B and C are not related
      to patient D. In patients E and F, we could identify only one mutant allele;
      Ala569Glu and Leu849His, respectively. All of the mutations identified are novel 
      except for the Arg642Cys mutation, which has been found in a Japanese GS patient.
      Although further in vitro study is required to prove that the mutations are
      responsible for GS, it is possible that Thr180Lys and Arg642Cys mutations might
      be common mutations in Japanese GS.
FAU - Monkawa, Toshiaki
AU  - Monkawa T
AD  - Department of Internal Medicine, School of Medicine, Keio University, Tokyo,
      Japan.
FAU - Kurihara, Isao
AU  - Kurihara I
AD  - Department of Internal Medicine, School of Medicine, Keio University, Tokyo,
      Japan.
FAU - Kobayashi, Kazuo
AU  - Kobayashi K
AD  - Department of Internal Medicine, School of Medicine, Keio University, Tokyo,
      Japan.
FAU - Hayashi, Matsuhiko
AU  - Hayashi M
AD  - Department of Internal Medicine, School of Medicine, Keio University, Tokyo,
      Japan.
FAU - Saruta, Takao
AU  - Saruta T
AD  - Department of Internal Medicine, School of Medicine, Keio University, Tokyo,
      Japan.
LA  - eng
PT  - Clinical Trial
PT  - Controlled Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Carrier Proteins)
RN  - 0 (Receptors, Drug)
RN  - 0 (SLC12A3 protein, human)
RN  - 0 (Sodium Chloride Symporters)
RN  - 0 (Solute Carrier Family 12, Member 3)
RN  - 0 (Symporters)
RN  - 0 (thiazide receptor)
SB  - IM
MH  - Adult
MH  - Bartter Syndrome/diagnosis/*genetics
MH  - Base Sequence
MH  - Carrier Proteins/*genetics
MH  - DNA Mutational Analysis
MH  - Female
MH  - *Frameshift Mutation
MH  - Gene Amplification
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Mutation, Missense
MH  - Pedigree
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Restriction Fragment Length
MH  - Receptors, Drug/*genetics
MH  - Reference Values
MH  - Sodium Chloride Symporters
MH  - Solute Carrier Family 12, Member 3
MH  - *Symporters
MH  - Syndrome
EDAT- 2000/01/05 00:00
MHDA- 2000/01/05 00:01
CRDT- 2000/01/05 00:00
PHST- 2000/01/05 00:00 [pubmed]
PHST- 2000/01/05 00:01 [medline]
PHST- 2000/01/05 00:00 [entrez]
AID - 11/1/65 [pii]
AID - 10.1681/ASN.V11165 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2000 Jan;11(1):65-70. doi: 10.1681/ASN.V11165.