• PMID: 32242295
• Gene Name: NR5A1
• Condition: Spermatogenic impairment
• Association: Associated
• Mutation: c.302 C>T, p.Arg101Gln rs750682280, c.368 C>G, p.Gly123Ala rs200163795, c.386 G>A, p.Pro129Leu rs200749741, c.787 C>T, p.Gly263Ser rs143355429, c.1052 G>A, p.Ala351Val rs759071081
• Population size: 1110
• Population details: 1100 subjects
• Sex: Male
• Infertility type: Male infertility

Development of a novel next-generation sequencing panel for diagnosis of quantitative spermatogenic impairment

Rocca MS, Msaki A, Ghezzi M, Cosci I, Pilichou K, Celeghin R, Foresta C, Ferlin A.

PURPOSE: To develop and assess a novel custom next-generation sequencing (NGS) panel for male infertility genetic diagnosis. METHODS: A total of 241 subjects with diagnosis of idiopathic infertility ranging from azoospermia to normozoospermia were sequenced by a custom NGS panel including AR, FSHB, FSHR, KLHL10, NR5A1, NANOS1, SEPT12, SYCP3, TEX11 genes. Variants with minor allele frequency < 1% were confirmed by Sanger sequencing. RESULTS: Nineteen missense variants were detected in 23 subjects with abnormal sperm count, whilst no variants were identified in normozoospermic men. Of identified variants, we prioritized variants classified as pathogenic and of uncertain significance (VUS) (63.1%, 12/19). No missense variants were found in males with normal seminal parameters (0/67). Therefore, the prevalence of variants was significantly higher in patients with spermatogenic impairment (16/174 vs 0/67, p = 0.007). CONCLUSION: This study confirms the utility to apply NGS panel for infertility diagnosis in order to find new genetic variants potentially linked to male infertility with much higher accuracy than standard tests suggested by guidelines. Indeed, based on biological significance, prevalence in the general population and clinical data of patients, it is plausible that identified variants in this study might be linked to quantitative spermatogenic impairment, although further studies are needed. FAU - Rocca, Maria Santa AU - Rocca MS AD - Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padua, Via Giustiniani, 2, 35128, Padova, Italy. FAU - Msaki, Aichi AU - Msaki A AD - Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padua, Via Giustiniani, 2, 35128, Padova, Italy. FAU - Ghezzi, Marco AU - Ghezzi M AD - Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padua, Via Giustiniani, 2, 35128, Padova, Italy. FAU - Cosci, Ilaria AU - Cosci I AD - Familial Cancer Clinic, Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy. FAU - Pilichou, Kalliopi AU - Pilichou K AD - Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padua, Padua, Italy. FAU - Celeghin, Rudy AU - Celeghin R AD - Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padua, Padua, Italy. FAU - Foresta, Carlo AU - Foresta C AD - Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padua, Via Giustiniani, 2, 35128, Padova, Italy. carlo.foresta@unipd.it.