Growth and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Gene. 2012 Jul 25;503(2):215-21. doi: 10.1016/j.gene.2012.04.080. Epub 2012 May 8.
Mutations of 3 beta hydroxysteroid dehydrogenase type II (HSD3B2) gene result in different clinical consequences. We explain a patient who demonstrated a salt wasting form of 3βHSD deficiency in infancy. Signs of hyponatremia and hyperkalemia were recognized in the infant with ambiguous genitalia and perineal hypospadias. The 46,XY male was genotyped by direct sequencing of HSD3B2 gene. Steroid profiles showed elevated concentration of 17 hydroxyprogesterone, and decrease in concentration of cortisol, and testosterone. Dehydroepiandrotone (DHEA) to androstenedione ratio had 6 fold increases. Direct sequencing of the patient revealed homozygous missense A82P mutation in exon 3. This mutation was confirmed by segregation analysis of the parents. Bioinformatic tools were used for in silico structural and functional analyses. Also, the pathological effect of the mutation was validated by different software. Alanine is a conserved amino acid in the membrane binding domain of the enzyme and proline substitution was predicted to destabilize the protein. This report may highlight the importance of the screening programs of the disorder in Iran.
3β 羟类固醇脱氢酶 II 型（HSD3B2）基因突变可导致不同的临床后果。我们解释了一例婴儿期表现为 3βHSD 缺乏盐耗竭型的患者。具有两性畸形和会阴型尿道下裂的婴儿出现低钠血症和高钾血症的迹象。46,XY 男性通过 HSD3B2 基因的直接测序进行基因分型。类固醇谱显示 17 羟孕酮浓度升高，皮质醇和睾酮浓度降低。脱氢表雄酮（DHEA）至雄烯二酮的比值增加了 6 倍。对患者的直接测序显示第 3 外显子存在纯合错义 A82P 突变。通过对父母的分离分析证实了该突变。生物信息学工具用于进行计算机结构和功能分析。此外，还通过不同的软件验证了突变的病理效应。丙氨酸是酶的膜结合域中的保守氨基酸，脯氨酸取代被预测会使蛋白质不稳定。本报告可能强调了在伊朗对该疾病进行筛查计划的重要性。
