A missense mutation (GGC[435Gly]-->AGC[Ser]) in exon 8 of the CYP11B2 gene inherited in Japanese patients with congenital hypoaldosteronism.
OBJECTIVE
To clarify the underlying molecular mechanism of corticosterone methyl oxidase type II (CMO II) deficiency, Japanese patients newly diagnosed with CMO II deficiency were investigated.


METHODS
We analyzed the patients' genomic DNA sequence on all 9 exons of the CYP11B2 gene. In addition, restriction fragment length polymorphism (RFLP) analysis and expression studies were performed.


RESULTS
The analysis showed that the patients homozygously retained a missense mutation, Gumacr;GC[435Gly]-->Aumacr;GC[Ser], in the CYP11B2 gene. Expression studies indicated that the steroid 18-hydroxylase/oxidase activities of the mutant enzyme were substantially reduced.


CONCLUSIONS
These results support the hypothesis that this mutation causes CMO II deficiency in the patients, and are in accordance with our theory that the partial loss of P-450(C18) activities causes CMO II deficiency.
Kuribayashi
Isao
I
Department of Medical Chemistry, Kochi Medical School, Kochi, Japan. kuribaya@kochi-ms.ac.jp
Kuge
Hideaki
H
Santa
Romero Jovel
RJ
Mutlaq
Aldahoodi Ziyad
AZ
Yamasaki
Naohito
N
Furuno
Takashi
T
Takahashi
Akio
A
Chida
Shoichi
S
Nakamura
Toshiro
T
Endo
Fumio
F
Doi
Yoshinori
Y
Onishi
Saburo
S
Shizuta
Yutaka
Y
D019943:Amino Acid Substitution; D044466:Asian People; D001483:Base Sequence; D019405:Cytochrome P-450 CYP11B2 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics; D006801:Humans; D006994:Hypoaldosteronism / Q000151:congenital* / Q000201:enzymology / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA
D019405:Cytochrome P-450 CYP11B2; C025352:corticosterone methyl oxidase II