Endocrine Abstracts

Introduction

Deficiency of 17- beta hydroxysteroid dehydrogenase 3 (17-HSD 3) is a rare autosomal recessive disorder which causes sexual ambiguity in fetuses with 46XY karyotype. Pathogenic mutations in the 17βHSD-3 gene (MIM# 264300) are associated with impaired sexual development of the 46, XY fetus. Here, we describe the clinical and genetic findings of a large family with several 46xy cases with a new mutation in 17-β-HSD3 gene in Qazvtn, Iran.

Case reports

Proposita was a 11-year-old girl who was referred for examination due to the infertility of her aunts. The external genitalia were completely female and had a short vaginal pouch. The testicles were not found on examination. She had palpable gonads in her inguinal area and at the age of two underwent bilateral orchiectomy. Other physical examinations were normal. In pelvic sonography, uterine and ovarian were not seen. Her peripheral blood karyotype was 46xy. Three of the patient’s aunts and the patient’s mother’s aunt also had had similar findings (Fig.1)

Figure 1: Pedigree

Method and Material

To determine the molecular etiology, whole-exome sequencing (WES) was performed.

Results

We identified a novel homozygous missense variation (c.731T>A, p. Ile244Lys) in HSD17B3 gene. This alteration changes Isoleucine to Lysine in exon 10. This variation – which has not been reported before – is predicted to be a variant of unknown significance (VUS) based on computational analysis.

References

1. M.D. Omrani, T. Adamovic, U. Grandell, S. Saleh-Gargari, A. Nordenskjöld. 17- -Hydroxysteroid Dehydrogenase Type 3 Deficiency in Three Adult Iranian Siblings. Sex Dev 2011 December; 5:273–276 DOI: 10.1159/000335006.

2. Al-Sinani A, Mula-Abed WA, Al-Kindi M, Al-Kusaibi G, Al-Azkawi H, Nahavandi N. A Novel Mutation Causing 17-β-Hydroxysteroid Dehydrogenase Type 3 Deficiency in an Omani Child: First Case Report and Review of Literature. Oman Med J. 2015 Mar; 30(2):129–34. doi: 10.5001/ omj.2015.27. PMID: 25960839; PMCID: PMC4412451.

3. Galli-Tsinopoulou A, Serbis A, Kotanidou EP, Litou E, Dokousli V, Mouzaki K, Fanis P, Neocleous V, Skordis N. 46, XY Disorder of Sex Development due to 17-Beta Hydroxysteroid Dehydrogenase Type 3 Deficiency in an Infant of Greek Origin. J Clin Res Pediatr Endocrinol. 2018 Mar 1; 10(1):74–78. doi: 10.4274/jcrpe.4829. Epub 2017 Jul 24. PMID: 28739554; PMCID: PMC5838376.