Clinical, Endocrine, and Molecular Genetic Findings in Patients with 17β-Hydroxysteroid Dehydrogenase Deficiency

Abstract

Mutations in the 17β-hydroxysteroid dehydrogenase (17β-HSD) type 3 gene are associated with the clinical findings of 17β-HSD deficiency. We investigated 5 patients of German descent with 46,XY karyotype and predominantly female phenotype. Androstenedione (A) and testosterone (T) levels in serum were determined before and after stimulation with human chorionic gonadotropin. DNA analysis of the whole coding region of the 17β-HSD type 3 gene was performed by PCR, single-strand conformation analysis, and direct sequencing. In all patients we found highly variable A and T levels before and after stimulation. However, the A-to-T ratio was abnormal in all cases suggestive of 17β-HSD deficiency. Molecular genetic analysis revealed mutations in all patients. We conclude that A and T levels may be highly variable in patients with 17β-HSD deficiency. Molecular genetic analysis of the 17β-HSD gene may support the diagnosis of this disorder.

17β-Hydroxysteroid Dehydrogenase Type 3 Deficiency: Diagnosis, Phenotypic Variability and Molecular Findings

“…(Mains et al, 2008). The majority are missense mutations inherited as homozygous or compound heterozygous mutations, occurring most frequent in exons 3,9,10 of the gene; 4 are splice junction abnormalities (Andersson et al, 1996;Boehmer et al, 1999), 1 is a small deletion (777-783), and 1 is a thymidine deletion resulting in a frame shift mutation which alters the amino acid sequence from codon position 187 onward with a premature termination in codon 226 (Boehmer et al, 1999;Twesten et al, 2000). Two missense mutations, the 239 G to A resulting in an Arg to Gln (R80Q) substitution, which is the most frequent alteration described in the Arab population living in the Gaza Strip (Boehmer et al,1999;Mains et al, 2008;Rosler et al, 1996), and the 238 C to T resulting in an Arg to Trp (R80W) substitution (Bilbao et al, 1998;Faienza et al, 2007) involve the same arginine residue in exon 3 at position 80.…”

Clinical, hormonal, and molecular-genetic characteristics of two cases of abnormal sex formation (ASF) in 46XY subjects caused by type 3 17-beta hydroxysteroid dehydrogenase deficiency

“…Стоит отметить, что, несмотря на рано проведенную орхипексию, у пациентов, воспиты-вающихся в мужском поле, сперматогенез всегда отсутствует. На данный момент нет ни одного опи-сания пациента с дефицитом 17ГСД3 и сохранной фертильностью [1,26].…”

The Basis of Gender Assignment in Disorders of Somatosexual Differentiation

“…These patients have an imbalance of androgenic steroids due to the enzymatic defect and show variable expression of virilization of different organs at the time of birth. Patients with 17β-hydroxysteroid dehydrogenase type 3 or 5α-reductase type 2 deficiency may have a female appearance with only slight signs of virilization of the external genitalia; however, internal sex-steroid-dependent organs such as epididymal structures may be well developed [10]. Furthermore, most of these patients undergo massive virilization at the time of puberty due to a surge of testicular androgen production with excessive formation of either androstenedione or testosterone as precursors of the enzyme defect.…”

“…In the 46,XY child, stimulation testing of the steroid-producing capacity of the gonad should be performed with human chorionic gonadotropin. It is of utmost importance that steroid values are determined in a laboratory with expertise in the variability of hormone levels in paediatric patients as well as their interference with fetal steroids [10]. Urinary steroid analysis may also be helpful in selected cases.…”