4 documents found, page 1 of 1
Diverse monogenic subforms of human spermatogenic failure
Nagirnaja, Liina; Lopes, Alexandra M.; Charng, Wu-Lin; Miller, Brian; Stakaitis, Rytis; Golubickaite, Ieva; Stendahl, Alexandra; Luan, TianpengchengNon-obstructive azoospermia (NOA) is the most severe form of male infertility and typically incurable. Defining the genetic basis of NOA has proven chal lenging, and the most advanced classification of NOA subforms is not based on genetics, but simple description of testis histology. In this study, we exome sequenced over 1000 clinically diagnosed NOA cases and identified a plausible recessive Mendelian cause i...
A de novo paradigm for male infertility
Oud, M.S.; Smits, R.M.; Smith, H.E.; Mastrorosa, F.K.; Holt, G.S.; Houston, B.J.; de Vries, P.F.; Alobaidi, B.K.S.; Batty, L.E.; Ismail, H.De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutations play an important role in severe male infertility and explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we utilize trio-based exome sequencing in a cohort of 185 infertile males and their unaffected parents. Following a systematic an...
Actionable secondary findings following exome sequencing of 836 non-obstructive...
Kasak, Laura; Lillepea, Kristiina; Nagirnaja, Liina; Aston, Kenneth I.; Schlegel, Peter N.; Gonçalves, João; Carvalho, Filipa; Moreno-Mendoza, DanielStudy question: What is the load, distribution and added clinical value of secondary findings (SFs) identified in exome sequencing (ES) of patients with non-obstructive azoospermia (NOA)? Summary answer: One in 28 NOA cases carried an identifiable, medically actionable SF. What is known already: In addition to molecular diagnostics, ES allows assessment of clinically actionable disease-related gene variants tha...
Variants in GCNA, X-linked germ-cell genome integrity gene, identified in men w...
Hardy, Jimmaline J.; Wyrwoll, Margot J.; Mcfadden, William; Malcher, Agnieszka; Rotte, Nadja; Pollock, Nijole C.; Munyoki, Sarah; Veroli, Maria V.Male infertility impacts millions of couples yet, the etiology of primary infertility remains largely unknown. A critical element of successful spermatogenesis is maintenance of genome integrity. Here, we present a genomic study of spermatogenic failure (SPGF). Our initial analysis (n=176) did not reveal known gene-candidates but identifed a potentially signifcant single-nucleotide variant (SNV) in X-linked ger...