| RRC ID |
18937
|
| 著者 |
Katsumata N, Shinagawa T, Horikawa R, Fujikura K.
|
| タイトル |
Novel intronic CYP21A2 mutation in a Japanese patient with classic salt-wasting steroid 21-hydroxylase deficiency.
|
| ジャーナル |
Metabolism
|
| Abstract |
Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder caused by the defective CYP21A2 gene that leads to various degrees of impaired secretion of both cortisol and aldosterone. In the present study, we analyzed the CYP21A2 gene in a Japanese male patient with 21-OHD and functionally characterized the mutant CYP21A2 gene. The patient presented with hypoglycemia and a salt-losing crisis during the neonatal period, and was diagnosed as having the salt-wasting form of 21-OHD based on the clinical and laboratory findings. Analysis of the CYP21A2 gene revealed that the patient is homozygous for a novel C to A conversion at -9 position of intron 9 (IVS9-9C>A) and that his parents are heterozygous for the IVS9-9C>A mutation. Transient expression of the IVS9-9C>A mutant CYP21A2 gene in COS-1 cells demonstrated that the mutation creates an aberrant splice acceptor site at -7 position of intron 9 and totally inactivates the authentic splice acceptor site of intron 9, which results in complete deficiency of 21-hydroxylase activity and loss of immunoreactive 21-hydroxylase protein. Clinical presentations of the patient as the severe salt-wasting form of 21-OHD are in good agreement with these results of the expression study. In conclusion, the patient is a homozygote for the novel intronic IVS9-9C>A mutation, which affects messenger RNA splicing and totally inactivates 21-hydroxylase to give rise to clinically manifest classic salt-wasting 21-OHD.
|
| 巻・号 |
59(11)
|
| ページ |
1628-32
|
| 公開日 |
2010-11-1
|
| DOI |
10.1016/j.metabol.2010.03.012
|
| PII |
S0026-0495(10)00102-2
|
| PMID |
20423741
|
| MeSH |
Adrenal Hyperplasia, Congenital / genetics*
Asians / genetics
Family
Genotype
Humans
Infant, Newborn
Introns / genetics
Male
Point Mutation*
RNA Splice Sites / genetics*
Salts / metabolism
Steroid 21-Hydroxylase / genetics*
|
| IF |
6.159
|
| 引用数 |
4
|
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
| リソース情報 |
| ヒト・動物細胞 |
COS-1(RCB0143) |
