Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 17, Pages -Publisher
MDPI
DOI: 10.3390/ijms231710026
Keywords
17-beta-hydroxysteroid dehydrogenase type 3; Disorder of Sex Development (DSD); pseudohermaphroditism; mutation
Funding
- Portuguese Foundation for Science and Technology (FCT) [UIDB/00709/2020]
- Programa Operacional Regional do Centro [CENTRO-08-5864-FSE-000039, CENTRO-01-0145-FEDER-000019]
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In this study, a child raised as a female was found to have compound heterozygous mutations in the HSD17B3 gene, which blocked the synthesis of testosterone and resulted in a Disorder of Sex Development. A total of 70 different HSD17B3 mutations have been reported so far, and these findings may be useful for the clinical management and genetic diagnosis of this disorder.
The 17-beta-hydroxysteroid dehydrogenase type 3 (17-beta-HSD3) enzyme converts androstenedione to testosterone and is encoded by the HSD17B3 gene. Homozygous or compound heterozygous HSD17B3 mutations block the synthesis of testosterone in the fetal testis, resulting in a Disorder of Sex Development (DSD). We describe a child raised as a female in whom the discovery of testes in the inguinal canals led to a genetic study by whole exome sequencing (WES) and to the identification of a compound heterozygous mutation of the HSD17B3 gene (c.608C>T, p.Ala203Val, and c.645A>T, p.Glu215Asp). Furthermore, we review all HSD17B3 mutations published so far in cases of 17-beta-HSD3 deficiency. A total of 70 different HSD17B3 mutations have so far been reported in 239 patients from 187 families. A total of 118 families had homozygous mutations, 63 had compound heterozygous mutations and six had undetermined genotypes. Mutations occurred in all 11 exons and were missense (55%), splice-site (29%), small deletions and insertions (7%), nonsense (5%), and multiple exon deletions and duplications (2%). Several mutations were recurrent and missense mutations at codon 80 and the splice-site mutation c.277+4A>T each represented 17% of all mutated alleles. These findings may be useful to those involved in the clinical management and genetic diagnosis of this disorder.
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