Molecular analysis of type II 3β-hydroxysteroid dehydrogenase gene in Japanese patients with classical 3β-hydroxysteroid dehydrogenase deficiency

• Published in: Human molecular genetics 1995-05, Vol.4 (5), p.969-971
• Main Authors: Tajima, Toshihiro, Fujieda, Kenji, Nakae, Jun, Shinohara, Nozomi, Yoshimoto, Masaaki, Baba, Tuneyoshi, Kinoshita, Ei-ichi, Igarashl, Yutaka, Oomura, Tutomu
• Format: Article
• Language: English
• Subjects: 3 beta -hydroxysteroid dehydrogenase; 3-Hydroxysteroid Dehydrogenases - deficiency; 3-Hydroxysteroid Dehydrogenases - genetics; adrenal glands; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Base Sequence; Biological and medical sciences; DNA - genetics; DNA Primers - genetics; Endocrinopathies; Female; Humans; Infant, Newborn; Isoenzymes - deficiency; Isoenzymes - genetics; Japan; Male; Malignant tumors; man; Medical sciences; Molecular Sequence Data; nucleotide sequence; Phenotype; Point Mutation; Polymerase Chain Reaction; steroids
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/4.5.969

Deficiency of 3 beta -hydroxysteroid dehydrogenase (3 beta -HSD) is a rare disorder and occurs in fewer than 5% of patients with adrenal hyperplasia. The enzyme is required for the biosynthesis of Delta 5 steroids,-pregnenolone, 17-OH pregnenolone, and dehydroepiandrosterone (DHEA)-to Delta 4 steroids, progesterone, 17-OH progesterone, and androstenedione in both the adrenals and the gonads. Deficiency of the enzyme results in decreased secretion of not only cortisol and aldosterone but also of progesterone, androgens and estrogens. In the classic form of the disorder, salt losing signs of varying degree are present in the neonate. Moreover affected boys exhibit incomplete virilization and hypospadias due to the lack of androgen synthesis in the testis. On the contrary, affected girls have normal sexual differentiation or are only mildly virilized. Recently, the structure and tissue-specific expression of human 3 beta -HSD genes encoding the type I and type II 3 beta -HSD isoenzymes were cloned, respectively. The complete nucleotide sequences of the type I and type II 3 beta -HSD gene demonstrated that their structural organization consists of four exons and three introns included within a DNA fragment of approximately 7.8 kb. Several mutations were present in the type II 3 beta -HSD gene from salt losing or nonsalt losing forms of classical 3 beta -HSD deficiency patients, whereas the type I 3 beta -HSD gene had no mutations in these patients. Here, to elucidate the molecular basis of Japanese patients with classical 3 beta -HSD deficiency, we investigated type II 3 beta -HSD genes of three sporadic cases and one siblings' case with classical 3 beta -HSD deficiency patients using polymerase chain reaction amplification (PCR) and direct sequencing.