Kalinchenko N Y, Makretskaya N A, Kolodkina A A, Ioutsi V A, Petrov V M, Tyulpakov A N
Endocrinology Research Centre.
Research Centre for Medical Genetics.
Probl Endokrinol (Mosk). 2024 Jan 9;70(6):91-98. doi: 10.14341/probl13415.
Deficiency of 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) is a rare variant of 46,XY disorders of sex development (DSD).
To give clinical, hormonal and molecular genetic characteristics of cases of 46,XY DSD associated with variants in the HSD17B3 gene.
The study included 310 patients with 46,XY DSD for the period from 2015 to 2019. The patients underwent a comprehensive examination, including a study of the steroid profile by high-performance liquid chromatography with tandem mass spectrometric detection, as well as a molecular genetic analysis using NGS.
According to the results of molecular genetic studies, biallelic nucleotide substitutions in the HSD17B3 gene were detected in 13 cases, which accounted for 4.2% of the total number of patients with 46,XY DSD. All 13 patients with biallelic variants in the HSD17B3 gene were registered as females. The ratio of androstenedione/testosterone concentrations in the blood in this group ranged from 1.4 to 8.9. 2 variants in the HSD17B3 gene were found in several patients: c.277+4A>T (on 6 chromosomes) and c.729_735del:p.V243fs (on 9 chromosomes). 4 novel variants have been identified. Monoallelic nucleotide substitutions in the HSD17B3 gene were detected in 7 cases, which accounted for 2.3% of the total number of patients with 46,XY DSD. External genitalia in this group corresponded to Prader stages 3-4. In 1 patient, a pathogenic variant c.277+4A>T was detected in the HSD17B3 gene, in other cases variants with uncertain significance were detected.
In the structure of 46,XY DSD, patients with biallelic variants in the HSD17B3 gene were identified in 4.2% of cases, with monoallelic variants - in 2.3% of cases. 4 novel variants were found in the HSD17B3 gene.
3型17β-羟基类固醇脱氢酶（HSD17B3）缺乏是46,XY性发育障碍（DSD）的一种罕见变异类型。
阐述与HSD17B3基因变异相关的46,XY DSD病例的临床、激素和分子遗传学特征。
该研究纳入了2015年至2019年期间的310例46,XY DSD患者。患者接受了全面检查，包括通过高效液相色谱串联质谱检测来研究类固醇谱，以及使用二代测序（NGS）进行分子遗传学分析。
根据分子遗传学研究结果，在13例患者中检测到HSD17B3基因的双等位核苷酸替换，占46,XY DSD患者总数的4.2%。所有13例HSD17B3基因双等位变异的患者均登记为女性。该组患者血液中雄烯二酮/睾酮浓度的比值在1.4至8.9之间。在几名患者中发现了HSD17B3基因的2种变异：c.277+4A>T（在6条染色体上）和c.729_735del:p.V243fs（在9条染色体上）。已鉴定出4种新变异。在7例患者中检测到HSD17B3基因的单等位核苷酸替换，占46,XY DSD患者总数的2.3%。该组患者的外生殖器对应于普拉德分期3-4期。在1例患者中检测到HSD17B3基因的致病性变异c.277+4A>T，在其他病例中检测到意义不明确的变异。
在46,XY DSD的结构中,4.2%的病例为HSD17B3基因双等位变异患者，2.3%的病例为单等位变异患者。在HSD17B3基因中发现了4种新变异。
