Lusa Letícia Gori, Lemos-Marini Sofia Helena Valente de, Soardi Fernanda Caroline, Ferraz Lucio Fabio Caldas, Guerra-Júnior Gil, Mello Maricilda Palandi de
Center for Molecular Biology and Genetic Engineering, Universidade Estadual de Campinas, SP, Brazil.
Arq Bras Endocrinol Metabol. 2010 Nov;54(8):768-74. doi: 10.1590/s0004-27302010000800018.
Type II 3β-hydroxysteroid dehydrogenase/Δ(5)-Δ(4)-isomerase (3β-HSD2), encoded by the HSD3B2 gene, is a key enzyme involved in the biosynthesis of all the classes of steroid hormones. Deleterious mutations in the HSD3B2 gene cause the classical deficiency of 3β-HSD2, which is a rare autosomal recessive disease that leads to congenital adrenal hyperplasia (CAH). CAH is the most frequent cause of ambiguous genitalia and adrenal insufficiency in newborn infants with variable degrees of salt losing. Here we report the molecular and structural analysis of the HSD3B2 gene in a 46,XY child, who was born from consanguineous parents, and presented with ambiguous genitalia and salt losing. The patient carries a homozygous nucleotide c.665C>A change in exon 4 that putatively substitutes the proline at codon 222 for glutamine. Molecular homology modeling of normal and mutant 3β-HSD2 enzymes emphasizes codon 222 as an important residue for the folding pattern of the enzyme and validates a suitable model for analysis of new mutations.
由HSD3B2基因编码的II型3β-羟基类固醇脱氢酶/Δ(5)-Δ(4)-异构酶（3β-HSD2）是参与所有类固醇激素生物合成的关键酶。HSD3B2基因中的有害突变会导致经典的3β-HSD2缺乏症，这是一种罕见的常染色体隐性疾病，会导致先天性肾上腺增生（CAH）。CAH是新生儿生殖器模糊和肾上腺功能不全最常见的原因，伴有不同程度的失盐。在此，我们报告了一名46,XY儿童HSD3B2基因的分子和结构分析，该儿童父母为近亲结婚，出生时生殖器模糊且有失盐症状。该患者在第4外显子中携带纯合核苷酸c.665C>A变化，推测该变化使密码子222处的脯氨酸被谷氨酰胺替代。正常和突变型3β-HSD2酶的分子同源性建模强调密码子222是该酶折叠模式的重要残基，并验证了一个适用于分析新突变的模型。
