NR5A1 gene variants in infertile Senegalese men: Discovery of a novel missense variant and genotype-phenotype correlation

Abstract

The NR5A1 gene, encoding Steroidogenic Factor 1 (SF-1), plays a critical role in sex differentiation and spermatogenesis. However, data on NR5A1 variants in sub-Saharan African populations remain limited. This exploratory pilot study aimed to identify and characterize NR5A1 variants in infertile Senegalese men and to assess genotype–phenotype correlations. We conducted a cross-sectional study in 23 infertile Senegalese men, and exons 2 –7 of NR5A1 were sequenced using the Sanger method. Detected variants were analyzed with in silico prediction tools and filtered for rarity (minor allele frequency < 1 %) using the gnomAD database. Genotype–phenotype associations were analyzed using Fisher’s exact test.

Eighty-three percent of patients harbored at least one NR5A1 variant. A novel heterozygous missense variant, c.584C > T (p.Ser195Phe), located in the hinge region of SF-1, was identified in three unrelated individuals presenting with micropenis, testicular hypotrophy, and azoospermia. Several previously described variants were also detected. Genotype–phenotype correlation analysis revealed significant associations between NR5A1 variants and spermatogenic failure, the most common clinical feature (60.8 %). These findings demonstrate substantial genetic variability in NR5A1 among Senegalese men with infertility, and identify a novel missense variant. Our study highlights the relevance of NR5A1 in male infertility screening and emphasizes the importance of incorporating African populations into reproductive genetics research.