Abstract
Corticosterone methyloxidase I (CMO I) deficiency is an autosomal recessive disorder of aldosterone biosynthesis. To determine further the molecular genetic basis of CMO I deficiency, a patient of Turkish origin that suffered from CMO I deficiency was studied. Nucleotide sequencing of the PCR-amplified exons from the genomic DNA of this patient revealed a single point mutation CTG (leucine) → CCG (proline) at codon 461 in exon 8 of CYP11B2, which is involved in the putative heme binding site of steroid 18-hydroxylase (P450(C18)). The expression study using a cDNA introducing the point mutation revealed that the amino acid substitution totally abolishes the P450(C18) enzyme activities required for conversion of 11-deoxycorticosterone to aldosterone, even though the mutant product was detected in the mitochondrial fraction of the transfected cells. These results suggest that this point mutation causes CMO I deficiency.
| Original language | English |
|---|---|
| Pages (from-to) | 382-385 |
| Number of pages | 4 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 234 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - May 19 1997 |
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All Science Journal Classification (ASJC) codes
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
CMO I deficiency caused by a point mutation in exon 8 of the human CYP11B2 gene encoding steroid 18-hydroxylase (P450(C18)). / Nomoto, Satoshi; Massa, Guy; Mitani, Fumiko; Ishimura, Yuzuru; Miyahara, Kaoru; Toda, Katsumi; Nagano, Isao; Yamashiro, Toshiyuki; Ogoshi, Shohei; Fukata, Jun Ichi; Onishi, Saburo; Hashimoto, Kozo; Doi, Yoshinori; Imura, Hiroo; Shizuta, Yutaka.
In: Biochemical and Biophysical Research Communications, Vol. 234, No. 2, 19.05.1997, p. 382-385.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CMO I deficiency caused by a point mutation in exon 8 of the human CYP11B2 gene encoding steroid 18-hydroxylase (P450(C18))
AU - Nomoto, Satoshi
AU - Massa, Guy
AU - Mitani, Fumiko
AU - Ishimura, Yuzuru
AU - Miyahara, Kaoru
AU - Toda, Katsumi
AU - Nagano, Isao
AU - Yamashiro, Toshiyuki
AU - Ogoshi, Shohei
AU - Fukata, Jun Ichi
AU - Onishi, Saburo
AU - Hashimoto, Kozo
AU - Doi, Yoshinori
AU - Imura, Hiroo
AU - Shizuta, Yutaka
PY - 1997/5/19
Y1 - 1997/5/19
N2 - Corticosterone methyloxidase I (CMO I) deficiency is an autosomal recessive disorder of aldosterone biosynthesis. To determine further the molecular genetic basis of CMO I deficiency, a patient of Turkish origin that suffered from CMO I deficiency was studied. Nucleotide sequencing of the PCR-amplified exons from the genomic DNA of this patient revealed a single point mutation CTG (leucine) → CCG (proline) at codon 461 in exon 8 of CYP11B2, which is involved in the putative heme binding site of steroid 18-hydroxylase (P450(C18)). The expression study using a cDNA introducing the point mutation revealed that the amino acid substitution totally abolishes the P450(C18) enzyme activities required for conversion of 11-deoxycorticosterone to aldosterone, even though the mutant product was detected in the mitochondrial fraction of the transfected cells. These results suggest that this point mutation causes CMO I deficiency.
AB - Corticosterone methyloxidase I (CMO I) deficiency is an autosomal recessive disorder of aldosterone biosynthesis. To determine further the molecular genetic basis of CMO I deficiency, a patient of Turkish origin that suffered from CMO I deficiency was studied. Nucleotide sequencing of the PCR-amplified exons from the genomic DNA of this patient revealed a single point mutation CTG (leucine) → CCG (proline) at codon 461 in exon 8 of CYP11B2, which is involved in the putative heme binding site of steroid 18-hydroxylase (P450(C18)). The expression study using a cDNA introducing the point mutation revealed that the amino acid substitution totally abolishes the P450(C18) enzyme activities required for conversion of 11-deoxycorticosterone to aldosterone, even though the mutant product was detected in the mitochondrial fraction of the transfected cells. These results suggest that this point mutation causes CMO I deficiency.
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U2 - 10.1006/bbrc.1997.6651
DO - 10.1006/bbrc.1997.6651
M3 - Article
C2 - 9177280
AN - SCOPUS:0031578241
VL - 234
SP - 382
EP - 385
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -