Novel and recurrent genetic variants associated with male and female infertility

Recently, the knowledge of the genetic basis of fertility disorders has expanded enormously, mainly thanks to the use of next-generation sequencing (NGS). However, the genetic cause of infertility, in the majority of patients, is still undefined. The aim was to identify novel and recurrent pathogenic/likely pathogenic variants in patients with isolated infertility or puberty delay using a targeted NGS technique. We have enrolled 41 patients (36 males and 5 females) with infertility problems or delayed puberty. We included the patients with hypogonadotropic hypogonadism (n = 12), hypergonadotropic hypogonadism (n = 15), abnormal sperm parameters (n = 10), androgen insensitivity syndrome (n = 3) and 46,XY gonadal dysgenesis (n = 1). Genetic tests were performed using targeted NGS panel of 35 genes implicated in fertility. Pathogenic or likely pathogenic variants potentially explaining the clinical phenotype were identified in 12 of 41 patients (29%). These included 9 of 12 patients (75%) with hypogonadotropic hypogonadism, 2 of 3 patients (66%) with androgen insensitivity syndrome, and the single patient with 46,XY gonadal dysgenesis. Among the 18 identified variants, 4 were novel (FGF8:p.Ala147Thr; SEMA3A:p.Arg544Cys; FGFR1:p.Thr141IlefsTer10; NSMF: p.Tyr242Cys), while 14 were recurrent. Our study expands the knowledge of the genetic basis of the infertility disorders and highlights the importance of genetic testing for proper diagnosis making and genetic counselling.