Mutation of 3β-hydroxysteroid dehydrogenase (3β-HSD) at the 3'-untranslated region is associated with adrenocortical insufficiency

Pan,Ying; Zhong,Shao; Hu,Ren-Ming; Gong,Wei

doi:10.3892/mmr.2012.1107

Mutation of 3β-hydroxysteroid dehydrogenase (3β-HSD) at the 3'-untranslated region is associated with adrenocortical insufficiency

Authors:
- Ying Pan
- Shao Zhong
- Ren-Ming Hu
- Wei Gong
View Affiliations

Affiliations: Department of Endocrinology, Kunshan People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu 215300, P.R. China, Department of Endocrine and Metabolic Diseases, Haishan Hospital Affiliated to Fudan University, Shanghai 200040, P.R. China
Published online on: September 28, 2012 https://doi.org/10.3892/mmr.2012.1107
Pages: 1305-1308

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

In the present study, we report the mutation of the 3β-hydroxysteroid dehydrogenase (3β-HSD) gene in a family suffering from adrenocortical insufficiency. The index patient was clinically diagnosed with adrenocortical insufficiency. Peripheral venous blood (5 ml) was collected from the proband and 5 members of his family, and genomic DNA was extracted. Exons 1, 2, 3 and 4 of the 3β-HSD gene and their flanking sequences were amplified by polymerase chain reaction (PCR). Some of the family members were examined by amplifying only exon 4. The PCR products were then purified and sequenced. The C to T homozygous mutation at nucleotide 1088 and C to G homozygous mutation at nucleotide 1132 within exon 4 of the 3β-HSD gene were found in the family members with abnormal phenotype. In the family members with normal phenotype, heterozygous mutations at the sites mentioned above were identified in the parents and Aunt 1, but not in Aunt 2 of the proband. In conclusion, a family with 3β-HSD deficiency was identified in the present study. The cause of the disease in the studied family appears to be two novel homozygous mutations in the 3β-HSD gene.

View Figures

View References

1	Rheaume E, Simard J, Morel Y, et al: Congenital adrenal hyperplasia due to point mutations in the type II 3β-hydroxysteroid dehydrogenase gene. Nature Genet. 1:239–245. 1992.
2	White PC and New MI: Molecular genetics of congenital adrenal hyperplasia. Baillieres Clin Endocrinol Metab. 2:941–965. 1988. View Article : Google Scholar : PubMed/NCBI
3	Rheaume E, Lachance Y, Zhao HF, et al: Structure and expression of a new complementary DNA encoding the almost exclusive 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase in human adrenals and gonads. Mol Endocrinol. 5:1147–1157. 1991. View Article : Google Scholar : PubMed/NCBI
4	Johannsen TH, Mallet D, Dige-Petersen H, et al: Delayed diagnosis of congenital adrenal hyperplasia with salt wasting due to type II 3beta-hydroxysteroid dehydrogenase deficiency. J Clin Endocrinol Metab. 90:2076–2080. 2005. View Article : Google Scholar : PubMed/NCBI
5	Bongiovanni AM, Eberlein WR, Goldman AS and New M: Disorders of adrenal steroid biogenesis. Recent Prog Horm Res. 23:375–449. 1967.PubMed/NCBI
6	Simard J, Rheaume E, Mebarki F, et al: Molecular basis of human 3β-hydroxysteroid dehydrogenase deficiency. J Steroid Biochem Mol Biol. 53:127–138. 1995.
7	Reiter JC, Leveau P, Tardy V, Forest MG and Morel Y: Diagnostic criteria for the diagnosis of 3β-hydroxysteroid dehydrogenase (3β-HSD) deficiency: lessons from hormonal and molecular studies in 2 girls presenting with premature pubarche. Horm Res. 53:762002.
8	Simard J, Moisan AM and Morel Y: Congenital adrenal hyperplasia due to 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase deficiency. Semin Reprod Med. 20:255–276. 2002. View Article : Google Scholar : PubMed/NCBI
9	Lutfallah C, Wang W, Mason JI, et al: Newly proposed hormonal criteria via genotypic proof for type II 3beta-hydroxysteroid dehydrogenase deficiency. J Clin Endocrinol Metab. 87:2611–2622. 2002.PubMed/NCBI
10	Ritzen EM, Lajic S and Wedell A: How can molecular biology contribute to the management of congenital adrenal hyperplasia? Horm Res. 53:34–37. 2000. View Article : Google Scholar : PubMed/NCBI
11	Luu the V, Lachance Y, Labrie C, et al: Full length cDNA structure and deduced amino acid sequence of human 3b-hydroxy-5-ene steroid dehydrogenase. Mol Endocrinol. 3:1310–1312. 1989.PubMed/NCBI
12	Cherradi N, Defay G and Chambaz EM: Dual subcellular localization of the 3β-hydroxysteroid dehydrogenase isomerase: characterization of the mitochondrial enzyme in the bovine adrenal cortex. J Steroid Biochem Mol Biol. 46:773–779. 1993.
13	Cherradi N, Defaye G and Chambaz EM: Characterization of the 3 beta-hydroxysteroid dehydrogenase activity associated with bovine adrenocortical mitochondria. Endocrinology. 134:1358–1364. 1994.
14	Sauer LA, Chapman JC and Dauchy RT: Topology of 3β-hydroxy-5-enesteroid dehydrogenase/D5-D4-isomerase in adrenal cortex mitochondria and microsomes. Endocrinology. 134:751–759. 1994.
15	Simard J, Durocher F, Mebarki F, et al: Molecular biology and genetics of the 3 beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase gene family. J Endocrinol. 150:S189–S207. 1996.PubMed/NCBI
16	Thomas JL, Evans BW, Blanco G, et al: Site-directed mutagenesis identifies amino acid residues associated with the dehydrogenase and isomerase activities of human type I (placental) 3β-hydroxysteroid dehydrogenase/isomerase. J Steroid Biochem Mol Biol. 66:327–334. 1998.PubMed/NCBI
17	Moisan AM, Ricketts ML, Tardy V, et al: New insight into the molecular basis of 3beta-hydroxysteroid dehydroxygenase deficiency: identification of eight mutation in the HSD3B2 gene eleven patients from seven new families and comparison of the functional properties of twenty-five mutant enzymes. J Clin Endocrinol Metab. 84:4410–4425. 1999.
18	Miller WL and Levine LS: Molecular and clinical advances in congenital adrenal hyperplasia. J Pediatr. 111:1–17. 1987. View Article : Google Scholar : PubMed/NCBI
19	Speiser PW, Dupont J, Zhu D, et al: Disease expression and molecular genotype in congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Invest. 90:584–595. 1992. View Article : Google Scholar : PubMed/NCBI
20	Zhang L, SakkaL-Alkaddour H, Chang YT, Yang X and Pang S: A new compound heterozygous frameshift mutation in the type II 3β-hydroxysteroid dehydrogenase (3β-HSD) gene caused salt-wasting 3β-HSD deficiency congenital adrenal hyperplasia. J Clin Endocrinol Metab. 81:291–295. 1996.
21	Moran C, Potter HD, Reyna R, Boots LR and Azziz R: Prevalence of 3 beta-hydroxysteroid dehydrogenase-deficient nonclassic adrenal hyperplasia in hyperandrogenic women with adrenal androgen excess. Am J Obstet Gynecol. 181:596–600. 1999. View Article : Google Scholar
22	Alos N, Mosian AM, Ward L, et al: A novel A10E homozygous mutation in the HSD3B2 gene causing severe salt-wasting 3beta-hydroxysteroid dehydrogenase deficiency in 46, XX and 46, XY French-Canadians: evaluation of gonadal function after puberty. J Clin Endocrinol Metab. 85:1968–1974. 2000.