• PMID: 29790874
• Gene Name: TEX14
• Condition: Nonobstructive azoospermia
• Association: Associated
• Mutation: c.C254A (p.Arg85Leu)
• Population size: 186
• Population details: 37 familial cases, 75 individuals with idiopathic NOA, 74 fertile men
• Sex: Male
• Infertility type: Male infertility
• Associated genes: NGS

Point-of-care whole-exome sequencing of idiopathic male infertility

Fakhro KA, Elbardisi H, Arafa M, Robay A, Rodriguez-Flores JL, Al-Shakaki A, Syed N, Mezey JG, Abi Khalil C, Malek JA, Al-Ansari A, Al Said S, Crystal RG.

PURPOSE: Nonobstructive azoospermia (NOA) affects 1% of the male population; however, despite state-of-the-art clinical assessment, for most patients the cause is unknown. We capitalized on an analysis of multiplex families in the Middle East to identify highly penetrant genetic causes. METHODS: We used whole-exome sequencing (WES) in 8 consanguineous families and combined newly discovered genes with previously reported ones to create a NOA gene panel, which was used to identify additional variants in 75 unrelated idiopathic NOA subjects and 74 fertile controls. RESULTS: In five of eight families, we identified rare deleterious recessive variants in CCDC155, NANOS2, SPO11, TEX14, and WNK3 segregating with disease. These genes, which are novel to human NOA, have remarkable testis-specific expression, and murine functional evidence supports roles for them in spermatogenesis. Among 75 unrelated NOA subjects, we identified 4 (~5.3%) with additional recessive variants in these newly discovered genes and 6 with deleterious variants in previously reported NOA genes, yielding an overall genetic etiology for 13.3% subjects versus 0 fertile controls (p = 0.001). CONCLUSION: NOA affects millions of men, many of whom remain idiopathic despite extensive laboratory evaluation. The genetic etiology for a substantial fraction of these patients (>50% familial and >10% sporadic) may be discovered by WES at the point of care. FAU - Fakhro, Khalid A AU - Fakhro KA AD - Translational Medicine, Sidra Medical and Research Center, Doha, Qatar. AD - Department of Genetic Medicine, Weill Cornell Medical College-Qatar, Doha, Qatar. FAU - Elbardisi, Haitham AU - Elbardisi H AD - Department of Urology, Hamada Medical Corporation, Doha, Qatar. FAU - Arafa, Mohamed AU - Arafa M AD - Department of Urology, Hamada Medical Corporation, Doha, Qatar. AD - Andrology Department, Cairo University, Egypt, Egypt. FAU - Robay, Amal AU - Robay A AD - Department of Genetic Medicine, Weill Cornell Medical College-Qatar, Doha, Qatar. FAU - Rodriguez-Flores, Juan L AU - Rodriguez-Flores JL AD - Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA. FAU - Al-Shakaki, Alya AU - Al-Shakaki A FAU - Syed, Najeeb AU - Syed N FAU - Mezey, Jason G AU - Mezey JG AD - Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA. FAU - Abi Khalil, Charbel AU - Abi Khalil C FAU - Malek, Joel A AU - Malek JA FAU - Al-Ansari, Abdulla AU - Al-Ansari A FAU - Al Said, Sami AU - Al Said S