Abstrakt
Background: Steroidogenic factor 1 (SF-1) is a key transcriptional regulator of the adrenal and gonadal development. Pathogenic variants in the NR5A1 gene are responsible for various degrees of insufficient virilisation, including gonadal and testicular dysgenesis with or without Müllerian remnants, ambiguous genitalia, mild and severe forms of hypospadias, micropenis, cryptorchidism, anorchia and male infertility.
We report a paternal pathogenic variant in the NR5A1 gene in a 46,XY 3-year-old patient with bifid scrotum, palpable testes, micropenis and proximal-perineal hypospadias. He was conceived by in vitro fertilisation (IVF).
The father of the patient had a similar phenotype prior to genital surgery. Methods: Exome sequencing was performed using Illumina's Twist Comprehensive Exome and Twist Mitochondrial DNA panel with a virtual panel of 130 genes associated with disorders of sex development (DSD).
Sanger sequencing was used to verify the results. Results: We identified a heterozygous pathogenic variant c.614dup p.(Gln206Thrfs*20) in the NR5A1 gene in the patient and his father.
Conclusion: The c.614dup variant has already been reported. However, 3 out of 4 reported patients were 46,XY DSD females.
The clinical information on the fourth patient was not included in the publication. We demonstrate that our patient and his father do not exhibit dysgenetic gonads typical for pathogenic variants in the NR5A1 gene, but rather hypoplastic, palpable testes.
We report that the patient's father, who carries a pathogenic variant, was able to conceive children by IVF.